Coil occlusion devices and systems and methods of using the same

ABSTRACT

Coil occluder devices and systems and methods of using the same. In an exemplary embodiment of an occluder system of the present disclosure, the occluder system comprises an occluder device comprising a coil having at least a first, uncompressed configuration and a second, compressed configuration, wherein the coil in the first, uncompressed configuration is configured to fit within a delivery mechanism sized and shaped to fit within a mammalian luminal organ, and wherein the coil in the second, compressed configuration is configured to occlude a mammalian luminal organ, and a delivery mechanism sized and shaped to fit within the mammalian luminal organ, the delivery mechanism configured to receive the coil in the first, uncompressed configuration within a lumen defined within the delivery mechanism.

PRIORITY

The present application (i) is related to, and claims the prioritybenefit of, U.S. Provisional Patent Application Ser. No. 61/543,330,filed Oct. 5, 2011, and (ii) is related to, claims the priority benefitof, and is a continuation-in-part of, U.S. Nonprovisional patentapplication Ser. No. 13/221,514, filed Aug. 30, 2011, which is relatedto, claims the priority benefit of, and is a continuation-in-part of,U.S. Nonprovisional patent application Ser. No. 13/092,803, filed Apr.22, 2011, which is related to, claims the priority benefit of, and is acontinuation-in-part of, U.S. Nonprovisional patent application Ser. No.13/124,512, filed Apr. 21, 2011, which is related to, claims thepriority benefit of, and is a U.S. §371 national stage application of,International Patent Application Serial No. PCT/US2008/087863, filedDec. 19, 2008. The contents of each of these applications areincorporated by reference in their entirety into this disclosure.

BACKGROUND

While direct surgical and percutaneous revascularization throughprocedures such as a percutaneous transluminal coronary angioplasty(“PTCA”) or coronary artery bypass grafting (“CABG”) remain the mainstayof treatment for patients with angina and coronary artery disease(“CAD”), there are many patients that are not amenable to suchconventional revascularization therapies. Because of this, much efforthas been made to find alternative methods of revascularization forischemic cardiac patients who are not candidates for revascularizationby conventional techniques. Such patients are generally identified as“no-option” patients because there is no conventional therapeutic optionavailable to treat their condition. As described in detail herein, thepresent disclosure provides various embodiments of devices to addresssuch chronic conditions.

In addition, and as described in detail herein, the present disclosureprovides various embodiments of devices that can be used acutely totreat patients with a number of conditions, such as S-T segment elevatedmyocardial infarction (STEMI) or cardiogenic shock or patients whorequire high risk percutaneous coronary intervention, until they canreceive more traditional therapy.

Currently, there are multiple specific conditions for which conventionalrevascularization techniques are known to be ineffective as a treatment.Two specific examples of such cardiac conditions include, withoutlimitation, diffuse CAD and refractory angina. Furthermore, a percentageof all patients diagnosed with symptomatic CAD are not suitable for CABGor PTCA. In addition and for various reasons discussed below, diabeticpatients—especially those with type 2 diabetes—exhibit an increased riskfor CAD that is not effectively treated by conventionalrevascularization techniques.

There is currently little data available on the prevalence and prognosisof patients with symptomatic CAD that is not amenable torevascularization through conventional methods. However, one studyindicated that out of five hundred (500) patients with symptomatic CADwho were considering direct myocardial revascularization andangiogenesis, almost twelve percent (12%) were not suitable for CABG orPTCA for various reasons. Furthermore, in general, patients withatherosclerotic involvement of the distal coronary arteries have highmortality and morbidity. For example, a study conducted on patientsindicated that, one (1) year after being diagnosed with atheroscleroticinvolvement of the distal coronary arteries, 39.2% of such patients hada cardiac-related death, 37.2% had an acute myocardial infarction, and5.8% had developed congestive heart failure. Overall, 82.2% of thepatients with atherosclerotic involvement of distal coronary arterieshad developed or experienced a significant cardiac event within one (1)year.

A. Diffuse CAD and Refractory Angina

CAD is typically not focal (i.e. limited to one point or a small regionof the coronary artery), but rather diffused over a large length of theentire vessel, which is termed “diffuse CAD.” Several studies indicatethat patients with a diffusely diseased coronary artery for whomstandard CABG techniques cannot be successfully performed constituteabout 0.8% to about 25.1% of all patients diagnosed with CAD.Furthermore, it is believed that diffuse CAD is much more common thanconventionally diagnosed because it is often difficult to detect by anangiogram due to the two-dimensional views.

Practitioners have realized that the quality of a patient's distalcoronary arteries is one of the critical factors related to a successfuloutcome of a surgical revascularization. As previously indicated, thereis considerable evidence that CABG for vessels having diffuse CADresults in a relatively poor outcome. In fact, studies have indicatedthat diffuse CAD is a strong independent predictor of death after a CABGprocedure. Further, as previously noted conventional revascularizationtechniques have also proven ineffective on a subgroup of patients withmedically refractory angina. In line with the aforementioned reasoning,this is likely because patients with medically refractory angina havesmall or diffusely diseased distal vessels that are not amenable toconventional revascularization therapies. Accordingly, patientsexhibiting diffuse CAD or medically refractory angina are oftenconsidered no-option patients and not offered bypass surgery, PTCA, orother conventional procedures.

B. Diabetes as a Risk Factor

Diabetes is an important risk factor for the development of CAD, diffuseor asymptomatic, and it has been estimated that approximatelyseventy-five percent (75%) of the deaths in diabetic patients are likelyattributed to CAD. It is estimated that 16 million Americans havediabetes, without only 10 million being diagnosed. Patients withdiabetes develop CAD at an accelerated rate and have a higher incidenceof heart failure, myocardial infarction, and cardiac death thannon-diabetics.

According to recent projections, the prevalence of diabetes in theUnited States is predicted to be about ten percent (10%) of thepopulation by 2025. Further, the increasing prevalence of obesity andsedentary lifestyles throughout developed countries around the world isexpected to drive the worldwide number of individuals with diabetes tomore than 330 million by the year 2025. As may be expected, the burdenof cardiovascular disease and premature mortality that is associatedwith diabetes will also substantially increase, reflecting in not onlyan increased amount of individuals with CAD, but an increased number ofyounger adults and adolescents with type 2 diabetes who are at a two- tofour-fold higher risk of experiencing a cardiovascular-related death ascompared to non-diabetics.

In addition to developing CAD at an accelerated rate, CAD in diabeticpatients is typically detected in an advanced stage, as opposed to whenthe disease is premature and symptomatic. Consequently, when diabeticpatients are finally diagnosed with CAD they commonly exhibit moreextensive coronary atherosclerosis and their epicardial vessels are lessamendable to interventional treatment, as compared to the non-diabeticpopulation. Moreover, as compared with non-diabetic patients, diabeticpatients have lower ejection fractions in general and therefore have anincreased chance of suffering from silent myocardial infarctions.

C. No-Option Patients

Some studies have shown that two-thirds (⅔rds) of the patients who werenot offered bypass surgery, because of diffuse CAD or otherwise, eitherdied or had a non-fatal myocardial infarction within twelve (12) months.Furthermore, patients diagnosed with diffuse CAD ran a two-foldincreased risk of in-hospital death or major morbidity, and theirsurvival rate at two (2) years was worse than those patients whoexhibited non-diffuse CAD or other complicating conditions. Aspreviously indicated, the majority of these patients are consideredno-option patients and are frequently denied bypass surgery as it isbelieved that CABG would result in a poor outcome.

Due to the increasing numbers of no-option patients and a trend incardiac surgery towards more aggressive coronary interventions, agrowing percentage of patients with diffuse CAD and other no-optionindications are being approved for coronary bypass surgery because, ineffect, there are no other meaningful treatment or therapeutic options.Some effects of this trend are that the practice of coronary bypasssurgery has undergone significant changes due to the aggressive use ofcoronary stents and the clinical profiles of patients referred for CABGare declining. As such, performing effective and successful coronarybypass surgeries is becoming much more challenging. Bypass graftingdiffusely diseased vessels typically requires the use of innovativeoperations such as on-lay patches, endarterectomies and more than onegraft for a single vessel. Patients with “full metal jackets” (ormultiple stents) are typically not referred to cardiac surgeons andoften end up as no-option patients despite the attempts of using theseinnovative surgeries.

In recent decades, the spectrum of patients referred for CABG are olderand are afflicted with other morbidities such as hypertension, diabetesmellitus, cerebral and peripheral vascular disease, renal dysfunction,and chronic pulmonary disease. In addition, many patients referred forCABG have advanced diffuse CAD and have previously undergone at leastone catheter-based intervention or surgical revascularization procedurethat either failed or was not effective. Because of this, the patient'svessels may no longer be graftable and complete revascularization usingconventional CABG may not be feasible. An incomplete myocardialrevascularization procedure has been shown to adversely affectshort-term and long-term outcomes after coronary surgery.

Due in part to some of the aforementioned reasons, reoperative CABGsurgery is now commonplace, accounting for over twenty percent (20%) ofcases in some clinics. It is well established that mortality forreoperative CABG operations is significantly higher than primaryoperations. As such, the risk profile of reoperative patients issignificantly increased and such patients are subjected to an increasedrisk of both in-hospital and long-term adverse outcomes.

Further, clinicians have also turned to unconventional therapies totreat non-option patients. For example, coronary endarterectomy (“CE”)has been used as an adjunct to CABG in a select group of patients withdiffuse CAD in order to afford complete revascularization. However,while CE was first described in 1957 as a method of treating CAD withoutusing cardiopulmonary bypass and CABG, this procedure has beenassociated with high postoperative morbidity and mortality rates and hasbeen afforded much scrutiny. Nevertheless, CE is the only therapeuticoption available for many no-option patients with diffuse CAD.

Similarly, because conventional therapies have proven ineffective or areunavailable to high risk patients, perioperative transmyocardialrevascularization (“TMR”) has been indicated for patients suffering frommedically refractory angina. TMR has proven effective for most patientssuffering from refractory angina; the mortality rate after TMR inpatients with stable angina ranges between about one to twenty percent(1-20%). Furthermore, in one study, TMR resulted in a higherperioperatively mortality rate in patients with unstable angina thanthose with stable angina (27% versus 1%). Some even report an operativemortality rate as low as twelve percent (12%). Patients who experienceangina and who cannot be weaned from intravenous nitroglycerin andheparin have a significantly higher operative mortality rate (16-27%versus 1-3%). Based on these findings, the clinical practice has been toavoid taking such patients to the operating room for TMR if at allpossible. The success of TMR is thought to be due to improved regionalblood flow to ischemic myocardium, but the precise mechanisms of itseffects remain unclear.

D. Acute Applications

When a coronary artery becomes blocked, the flow of blood to themyocardium stops and the muscle is damaged. This process is known asmyocardial infarction (MI). An MI can damage the myocardium, resultingin a scarred area that does not function properly. MI has an annualincidence rate of 1.5 million in the US and is the primary driver ofroughly 500,000 cases of mortality and high morbidity rates in CADpatients. Immediate reperfusion of the myocardium following MI isclinically desirable to preserve as much heart tissue as possible.Current revascularization options include thrombolytic medications,percutaneous coronary intervention (PCI), or coronary artery bypassgraft (CABG). While thrombolytic compounds can be administered swiftlyin an acute care facility, the vast majority of MI patients require aPCI or CABG to adequately restore reliable blood flow to the hearttissue. Both of these revascularization techniques are clinically safeand effective, however, they require specialized staff and facilities,which are not available at all acute care facilities, or not availablesoon enough to preserve enough myocardial tissue in the wake of an MI. Asignificant effort has been undertaken in recent years to speed MIpatients to the cath lab for PCI upon presenting, but these programs arenot available everywhere, and even where available, do not often meetthe 90 minute target of door to balloon time.

In the US, nearly 75,000 CAD patients annually present withatherosclerosis of the left main coronary artery (LMCA). The LMCAdelivers oxygenated blood to 75% or more of the myocardium. Anuntreated, diseased LMCA results in 20% 1-year and 50% 7- to 10-yearmortality rates. Historically, PCI of the LMCA (LMPCI) has been deemedtoo risky, however, recent advances in technique and tools have begun toallow an expanded LMCA patient population for PCI, especially in certainpatient conditions where PCI is preferable to CABG (e.g., patients whoare aging, delicate, and/or in critical condition).

The risks of LMPCI include prolonged myocardial ischemia from ballooninflations, “no-reflow phenomenon” (2-5% incidence rate), or coronaryartery dissections (30% incidence rate). Existing circulatory supportdevices used to address these hemodynamic issues, such as theintra-aortic balloon pump (IABP) and left ventricle circulatory supportdevices (e.g., Impella 2.5), are unable to sufficiently meet themyocardium oxygen demands even though cardiac pumping mechanics areimproved. The assistance from these devices is limited further duringno-reflow and coronary artery dissection events. In addition, theclinically superior left ventricle circulatory support devices arecomplicated to use and require dedicated training and facilities, whichhas prevented wide-spread clinical adoption.

There are over 35,000 cardiogenic shock (CS) patients each year in theUS. This condition severely complicates an MI event with in-hospitalmortality rates exceeding 50 percent. PCI is the standard of care forthese acute patients; however, the CS patient must be stabilized priorto intervention, according to ACC/AHA guidelines, using a short-termcirculatory support device as a bridge. An IABP or left ventriclecirculatory support device (e.g. Impella 2.5) can currently be utilizedin these cases to stabilize the heart while awaiting revascularization.

The 200,000 S-T segment elevated MI (STEMI) patients per year in the USrequire immediate reperfusion of the myocardium. Thrombolyticmedications are administered as the primary revascularization technique,however, 70 percent of those receiving thrombolysis fail to respond.Furthermore, 10 percent of those that initially respond to thrombolysisexperience reocclusion while still an in-patient. These STEMI patientsrequire clinically superior rescue PCI, as opposed to repeatedthrombolysis.

Because only 1,200 out of 5,000 acute care hospitals are capable ofperforming PCI (and even fewer are capable of CABG), nearly 60 percentof STEMI patients do not achieve the required 90 minute time-frame forrevascularization.

While awaiting revascularization, IAPB currently is the preferredcirculatory assist device and is indicated for use by critical care unit(CCU), intensive care unit (ICU) and emergency medicine (ER) physiciansin a variety of clinical settings. However, the IABP's use in MI eventsremains at less than 5 percent of cases due to complicated training anddevice-related malfunctions in 12-30% of all cases.

Circulatory support devices used in these cases have two major problems:inability to adequately augment blood flow in flow-limitingatherosclerotic coronary arteries to a damaged myocardium, and 12-30%device complication incidence rates, including peripheral ischemia,compartment syndrome, infection, hematological issues, and mechanicalissues.

Certain patients requiring coronary bypass surgery, for example, may nothave sufficient vasculature suitable for grafting in connection with thesurgery. Said vasculature would need to be sufficiently strong as towithstand the relatively high arterial pressures as compared to therelatively low venous pressures.

In view of the same, devices, systems, and methods useful to facilitatearterialization of veins for use in connection with bypass surgeries,for example, would be well-received in the marketplace.

BRIEF SUMMARY

In an exemplary embodiment of an occluder device of the presentdisclosure, the occluder device comprises a coil having at least afirst, uncompressed (or expanded) configuration and a second, compressed(or retracted) configuration, wherein the coil in the first,uncompressed (or expanded) configuration is capable of fitting within adelivery mechanism sized and shaped to fit within a mammalian luminalorgan, and wherein the mammalian luminal organ is occluded when the coilis positioned therein in the second, compressed (or retracted)configuration.

In an exemplary embodiment of an occluder system of the presentdisclosure, the system comprises an exemplary occluder device of thepresent disclosure, and a delivery mechanism sized and shaped to fitwithin a mammalian luminal organ, the delivery mechanism configured toreceive an exemplary occluder device therethrough.

In an exemplary embodiment of an occluder system of the presentdisclosure, the system comprises a coil having at least a first,uncompressed configuration and a second, compressed configuration, adelivery mechanism sized and shaped to fit within a mammalian luminalorgan, the delivery mechanism configured to receive the coil within alumen defined within the delivery mechanism, and a pusher configured tofit within the lumen of the delivery mechanism and further configured tofacilitate placement of the coil within the mammalian luminal organ. Inanother embodiment, the system further comprises a guidewire configuredto fit within the mammalian luminal organ and further configured to fitwithin the lumen of the delivery mechanism. In yet another embodiment,the coil in the first, uncompressed configuration is capable of fittingwithin the delivery mechanism, and the coil in the second, compressedconfiguration is capable of occluding a mammalian luminal organ. In anadditional embodiment, the coil is capable of changing from the first,uncompressed configuration to the second, compressed configuration whenthe coil is engaged by the pusher.

In an exemplary embodiment of an occluder system of the presentdisclosure, the pusher comprises a shaft and a tip. In an additionalembodiment, the tip is relatively or completely circular in shape andconfigured to prevent the coil from moving past the pusher within thedelivery mechanism. In yet an additional embodiment, the deliverymechanism comprises a delivery catheter having a wall and defining alumen therethrough. In another embodiment, the delivery mechanism issized and shaped to fit within a patient's vein. In yet anotherembodiment, the coil is capable of changing from the first, uncompressedconfiguration to the second, compressed configuration and back to thefirst, uncompressed configuration.

In an exemplary embodiment of an occluder device of the presentdisclosure, the occluder device comprises a coil having at least afirst, uncompressed configuration and a second, compressedconfiguration, wherein the coil in the first, uncompressed configurationis capable of fitting within a delivery mechanism sized and shaped tofit within a mammalian luminal organ, and wherein the coil in thesecond, compressed configuration is capable of occluding a mammalianluminal organ. In another embodiment, the coil is capable of changingfrom the first, uncompressed configuration to the second, compressedconfiguration when the coil is engaged by a pusher sized and shaped tofit within the delivery mechanism. In yet another embodiment, the pushercomprises a shaft and a tip. In an additional embodiment, the tip isrelatively or completely circular in shape and configured to prevent thecoil from moving past the pusher within the delivery mechanism.

In an exemplary embodiment of an occluder device of the presentdisclosure, the delivery mechanism comprises a delivery catheter havinga wall and defining a lumen therethrough. In an additional embodiment,the delivery mechanism is sized and shaped to fit within a patient'svein. In yet an additional embodiment, the coil is capable of changingfrom the first, uncompressed configuration to the second, compressedconfiguration and back to the first, uncompressed configuration. Inanother embodiment, the coil is capable of changing from the first,uncompressed configuration to the second, compressed configuration whenthe coil is engaged by a pusher sized and shaped to fit within thedelivery mechanism, wherein the delivery mechanism comprises a deliverycatheter having a wall and defining a lumen therethrough, wherein thedelivery mechanism is sized and shaped to fit within a patient's vein,and wherein the coil is capable of changing from the first, uncompressedconfiguration to the second, compressed configuration and back to thefirst, uncompressed configuration.

In an exemplary embodiment of an occluder device of the presentdisclosure, the coil comprises a material selected from the groupconsisting of nitinol and stainless steel. In an additional embodiment,the coil is at least partially coated by a material selected from thegroup consisting of polytetrafluoroethylene, polyethylene terephthalate,and polyurethane. In another embodiment, the coil is radiopaque.

In an exemplary embodiment of a method of using an occluder device ofthe present disclosure, the method comprising the steps of introducingan exemplary occlusion device of the present disclosure into a patient'sbody, the occlusion device positioned within a lumen of an exemplarydelivery mechanism of the present disclosure, advancing at least part ofthe delivery mechanism to a desired location within the patient's body,advancing the exemplary occluder device directly into a luminal organwithin the patient's body, and compressing the exemplary occluder devicewithin the luminal organ to occlude the luminal organ. In anotherembodiment, the introducing step includes the steps of introducing aguidewire into the patient's body, advancing a delivery mechanism of thepresent disclosure into the patient's body over the guidewire, andremoving the guidewire from the patient's body. In yet anotherembodiment, the luminal organ comprises a vein. In an additionalembodiment, the step of advancing the exemplary occluder device directlyinto the luminal organ is performed by using a pusher positioned withinthe delivery mechanism to advance the exemplary occluder device. In yetan additional embodiment, the step of compressing the exemplary occluderdevice within the luminal organ is performed by using a pusherpositioned within the delivery mechanism to compress the exemplaryoccluder device

In an exemplary embodiment of a method of using an occluder device ofthe present disclosure, the compressing step is performed to facilitatea configuration change of the exemplary occluder device from a firstuncompressed or otherwise non-occlusive configuration to a secondcompressed or otherwise occlusive configuration. In an additionalembodiment, the method further comprises the step of withdrawing thedelivery mechanism and the pusher from the patient's body. In yet anadditional embodiment, the method further comprises the steps ofexcising an arterialized vein from the patient's body, the arterializedvein located at or near the compressed exemplary occluder device, andgrafting the arterialized vein into the patient's arterial system. Inanother embodiment, the method further comprises the step of performinga retroperfusion procedure while the exemplary occluder device iscompressed within the luminal organ and/or after the step of excisingthe arterialized vein. In yet another embodiment, the step of advancingat least part of the delivery mechanism to a desired location within thepatient's body is performed by advancing at least part of the deliverymechanism into a heart of the patient, through a coronary sinus, andinto a cardiac vein. In an additional embodiment, the step of advancingthe exemplary occluder device directly into the luminal organ within thepatient's body is performed by advancing the exemplary occluder devicedirectly into the cardiac vein.

BRIEF DESCRIPTION OF THE DRAWINGS

The disclosed embodiments and other features, advantages, anddisclosures contained herein, and the matter of attaining them, willbecome apparent and the present disclosure will be better understood byreference to the following description of various exemplary embodimentsof the present disclosure taken in conjunction with the accompanyingdrawings, wherein:

FIG. 1 shows a side view of a catheter for placement within an arterialvessel and that may be used to deliver retroperfusion therapy, accordingto at least one embodiment of the present disclosure;

FIG. 2A shows a side view of the catheter of FIG. 1 in a collapsedposition, according to at least one embodiment of the presentdisclosure;

FIG. 2B shows a side view of the catheter of FIG. 1 in an extendedposition, according to at least one embodiment of the presentdisclosure;

FIG. 3 shows a side view of an autoretroperfusion system positioned todeliver retroperfusion therapy to a heart, according to at least oneembodiment of the present disclosure;

FIGS. 4A and 4B show perspective views of the distal end of a venouscatheter used in the autoretroperfusion system of FIG. 3, according toat least one embodiment of the present disclosure;

FIG. 5 shows the components of an autoretroperfusion system that can beused to deliver retroperfusion therapy to ischemic tissue, according toat least one embodiment of the present disclosure;

FIG. 6 shows a view of the base and diaphragmatic surface of a heartwith the distal ends of two components of the autoretroperfusion systemof FIG. 5 positioned therein such that the autoretroperfusion system candeliver simultaneous selective autoretroperfusion therapy thereto,according to at least one embodiment of the present disclosure;

FIG. 7 shows a flow chart of a method for delivering autoretroperfusiontherapy, according to at least one embodiment of the present disclosure;

FIG. 8A shows a side view of the catheter of FIG. 1 in a collapsedposition within an introducer, according to at least one embodiment ofthe present disclosure;

FIG. 8B, shows a side view of the catheter of FIG. 1 being introducedvia an introducer into an arterial vessel, according to at least oneembodiment of the present disclosure;

FIGS. 8C and 8D show side views of the introducer of FIG. 8A beingremoved from an arterial vessel, thereby deploying the projectioncannula of the catheter of FIG. 1, according to at least one embodimentof the present disclosure;

FIG. 8E shows a side view of the catheter of FIG. 1 anchored within anarterial vessel through the use of an expandable balloon, according toat least one embodiment of the present disclosure;

FIG. 9 shows a schematic view of the autoretroperfusion system of FIG. 5as applied to a heart, according to at least one embodiment of thepresent disclosure;

FIG. 10 shows a schematic view of the autoretroperfusion system of FIG.5 as applied to a heart, according to at least one embodiment of thepresent disclosure;

FIG. 11 shows a schematic view of a step of the method of FIG. 7 as themethod is applied to a heart, according to at least one embodiment ofthe present disclosure;

FIG. 12 shows a flow chart of a method for delivering simultaneouslyselective autoretroperfusion therapy, according to at least oneembodiment of the present disclosure;

FIG. 13 shows a schematic view of a step of the method of FIG. 12 as themethod is applied to a heart, according to at least one embodiment ofthe present disclosure;

FIG. 14 shows a schematic view of a step of the method of FIG. 12 as themethod is applied to a heart, according to at least one embodiment ofthe present disclosure;

FIG. 15 shows an exemplary retroperfusion system, according to at leastone embodiment of the present disclosure;

FIG. 16 shows a portion of an exemplary retroperfusion system, accordingto at least one embodiment of the present disclosure; and

FIG. 17 shows a block diagram of components of an exemplaryretroperfusion system coupled to a blood supply, according to at leastone embodiment of the present disclosure;

FIG. 18 shows a schematic of the retroperfusion system showing thearterial and retroperfusion catheters, according to a study inconnection with the present disclosure;

FIG. 19 shows a diagram of steps of an exemplary method of organperfusion, according to at least one embodiment of the presentdisclosure;

FIG. 20 shows an exemplary occluder device in a first configurationwithin a delivery mechanism, according to an exemplary embodiment of thepresent disclosure;

FIG. 21 shows a an exemplary occluder device in a second configurationwithin a patient's luminal organ, according to an exemplary embodimentof the present disclosure;

FIG. 22A shows an exemplary occluder device in a first configurationwithin a delivery mechanism within a patient's coronary vein, accordingto an exemplary embodiment of the present disclosure;

FIG. 22B shows a an exemplary occluder device in a second configurationwithin a patient's coronary vein, according to an exemplary embodimentof the present disclosure;

FIG. 22C shows an exemplary occluder device in a first configurationwithin a delivery mechanism positioned through a patient's heart andwithin a patient's coronary vein, according to an exemplary embodimentof the present disclosure;

FIG. 23 shows a block diagram of a system having an exemplary occluderdevice, according to an exemplary embodiment of the present disclosure;and

FIG. 24 shows a diagram of method steps, according to an exemplaryembodiment of the present disclosure.

An overview of the features, functions and/or configurations of thecomponents depicted in the various figures will now be presented. Itshould be appreciated that not all of the features of the components ofthe figures are necessarily described. Some of these non-discussedfeatures, such as various couplers, etc., as well as discussed featuresare inherent from the figures themselves. Other non-discussed featuresmay be inherent in component geometry and/or configuration.

DETAILED DESCRIPTION

The embodiments discussed herein include devices, systems, and methodsuseful for providing selective autoretroperfusion to the venous system.In addition, and with various embodiments of devices and systems of thepresent disclosure, said devices and/or systems can also be used toachieve a controlled arterialization of the venous system. Furthermore,various devices, systems, and methods for occluding a vessel areprovided herein. For the purposes of promoting an understanding of theprinciples of the present disclosure, reference will now be made to theembodiments illustrated in the drawings, and specific language will beused to describe the same. It will nevertheless be understood that nolimitation of the scope of this disclosure is thereby intended.

The devices, systems and methods disclosed herein can be used to safelyand selectively arterialize venous vessels in order to decrease thestress thereon and prevent rupture of the same. Accordingly, through theuse of the devices, systems and methods disclosed herein, long-termautoretroperfusion of oxygenated blood through the coronary venoussystem can be achieved, thereby providing a continuous supply ofoxygen-rich blood to an ischemic area of a tissue or organ. While thedevices, systems and methods disclosed herein are described inconnection with a heart, it will be understood that such devices,systems and methods are not limited in their application solely to theheart and the same may be used in connection with any ischemic tissueand/or organ in need of an oxygen-rich blood supply.

Selective auto-retroperfusion (SARP) can be indicated for both chronicand acute applications, and exemplary catheters 10 and/or systems 100 ofthe present disclosure (and as referenced in further detail herein) canbe used in connection therewith. References to “acute” for SARPapplications are used generally to indicate the amount of time that anexemplary catheter 10 and/or system 100 of the present disclosure may bein use on a given patient. In at least one embodiment, catheter 10and/or system 100, or portions thereof, will be sterile and intended fordisposal after a single use. In at least one embodiment of a system 100useful in connection with an acute indication, use of system 100 couldbe limited to less than 24 hrs.

Now referring to FIG. 1, a side view of a catheter 10 is shown. Thecatheter 10 is configured to be placed within an arterial vessel andcomprises a flexible, elongated tube having a proximal end 12, a distalend 14 and at least one lumen 15 extending between the proximal end 12and the distal end 14. The dimensions of the catheter 10 may varydepending on the particulars of a specific patient or with respect tothe artery to be cannulated. For example and without limitation, wherethe catheter 10 is used to in a system for autoretroperfusion of thecoronary sinus, the catheter 10 may comprise a diameter of about 2.7millimeters to about 4 millimeters (about 8 Fr to about 12 Fr).Furthermore, the at least one lumen 15 of the catheter 10 comprises asufficient diameter such that blood can flow therethrough. In addition,the catheter 10 may be comprised of any appropriate material, includingwithout limitation, polyurethane or silicone rubber. Furthermore, thecatheter 10 may be coated with heparin or any other suitableanti-coagulant such that the catheter 10 may be placed within a vesselfor an extended period of time without inhibiting blood flow due tocoagulation.

The distal end 14 of the catheter 10 is configured to allow arterialblood to flow therethrough and into the at least one lumen 15 of thecatheter 10. Similarly, the proximal end 12 of the catheter 10 isconfigured to allow blood within the at least one lumen 15 to flow outof the catheter 10. Accordingly, when the catheter 10 is positionedwithin an arterial vessel, the oxygenated blood is allowed to flow intothe catheter 10 through the distal end 14 of the catheter 10, throughthe at least one lumen 15, and out of the catheter 10 through theproximal end 12 of the catheter 10. In this manner, placement of thecatheter 10 within a vessel does not inhibit the flow of blood throughthe vessel or significantly affect the pressure of the blood flow withinthe vessel.

As shown in FIG. 1, the catheter 10 further comprises a projectioncannula 16 that extends from the proximal end 12 of the catheter 10 andforms a Y-shaped configuration therewith. The projection cannula 16comprises a flexible tube of material that is appropriate for insertionwithin a vessel and placement within an opening in a vessel wall.Furthermore, the projection cannula 16 comprises at least one lumen 18,a proximal end 20, and a distal end 22. The distal end 22 of theprojection cannula 16 is coupled with the body of the catheter 10 andconfigured to allow the lumen 18 of the projection cannula 16 tocommunicate with at least one of the at least one lumens 15 of thecatheter 10. Accordingly, when blood flows through the at least onelumen of the catheter 10, a portion of the blood flow enters the lumen18 of the projection cannula 16 through the distal end 22 thereof andflows out through the proximal end 20 of the projection cannula 16. Inthis manner, the catheter 10 is capable of bifurcating the flow of bloodthrough the vessel in which it is inserted and routing some of thatblood flow out of the vessel and to another location.

This bifurcation can be exploited to modify the pressure of the bloodflowing through the projection cannula 16 and/or through the proximalend 12 of the catheter 10 by manipulating the dimensions of theprojection cannula 16 and the body of the catheter 10. For example, andwithout limitation, if the diameter of the projection cannula 16 is lessthan the diameter of the at least one lumen 15 of the catheter 10, themajority of the blood will flow through the proximal end 12 of thecatheter 10 and the pressure of the remaining blood that flows throughthe smaller projection cannula 16 will necessarily be reduced.Predictably, the smaller the diameter of the lumen 18 of the projectioncannula 16, the greater the pressure drop that can be achieved in theblood flowing through the lumen 18 of the projection cannula 16.Accordingly, with respect to the catheter's 10 application toautoretroperfusion therapies, the projection cannula 16 can be used tore-route blood flow from an artery to a vein while simultaneouslyachieving the necessary pressure drop in the re-routed blood between thearterial system and unarterialized venous system. Moreover, the catheter10 is capable of maintaining substantially normal blood flow through theartery in which it is housed as the arterial blood not re-routed throughthe projection cannula 16 is allowed to flow through the open proximalend 12 of the catheter 10 and back into the artery in the normalantegrade fashion.

Due to the configuration of the projection cannula 16 and the materialof which it is comprised, the projection cannula 16 is capable ofhingedly moving relative to the body of the catheter 10 between acollapsed position and an extended position. Now referring to FIGS. 2Aand 2B, the projection cannula 16 is shown in the collapsed position(FIG. 2A) and in the extended position (FIG. 2B). When the projectioncannula 16 is in the collapsed position, the projection cannula 16 ispositioned substantially parallel with the body of the catheter 10.Alternatively, when the projection cannula 16 is in the extendedposition, the projection cannula 16 is positioned such that theprojection cannula 16 forms an angle θ with the proximal end 12 of thecatheter 10. The value of angle θ may be selected depending on thedesired application of the catheter 10. For example, in at least oneembodiment, the angle θ may comprise any value ranging between about 15°and about 90°. In another example, the angle θ may comprise about 45°when the projection cannula 16 is in the extended position.

The projection cannula 16 is biased such that, when it is not subject toa downward force, the projection cannula 16 rests in the expandedposition. Conversely, when a downward force is applied to the projectioncannula 16 by way of an introducer or otherwise, the projection cannula16 moves into and remains in the collapsed position until the downwardforce is removed. In this manner, the projection cannula 16 may beintroduced into a vessel in the collapsed position through the use of anintroducer or shaft and thereafter move into the expanded position whenthe catheter 10 is properly positioned within the vessel and theintroducer or shaft is removed.

Optionally, as shown in FIG. 1, the catheter 10 may further comprise anexpandable balloon 58 coupled with an intermediary portion of theexternal surface of the catheter 10 such that the expandable balloon 58encases the catheter 10 and the distal end 22 of the projection cannula18. The expandable balloon 58 may be any expandable balloon 58 that isappropriate for insertion within a vessel and may comprise any materialsuitable for this function, including without limitation, polyethylene,latex, polyestherurethane, polyurethane, sylastic, silicone rubber, orcombinations thereof. In operation, the expandable balloon 58 can beused to anchor the catheter 10 in a desired position within a vesselwall and prevent leakage from the opening in the vessel wall throughwhich the projection cannula 16 traverses.

The expandable balloon 58 is capable of being controlled by a cliniciansuch that it can inflate and/or deflate to the proper size. The sizingof the expandable balloon 58 will differ between patients andapplications. The expandable balloon 58 may be in fluid communicationwith a balloon inflation port 62 through a secondary lumen 60 within thelumen 18 of the projection cannula 16. Alternatively, the expandableballoon 58 may be in fluid communication with the balloon inflation port62 through a tube or other means that is positioned within the lumen 18of the projection cannula 16 as shown in FIG. 1. The balloon port 62 maybe positioned subcutaneously or otherwise such that a clinician caneasily access the balloon port 62 when the catheter 10 is positionedwithin a vessel. In this manner the balloon port 62 can be accessed by aclinician, subcutaneously, percutaneously or otherwise, and used toinflate or deflate the expandable balloon 58 with no or minimal invasionto the patient.

Now referring to FIG. 3, an autoretroperfusion system 100 is shownpositioned to allow arterial blood to irrigate the coronary sinus of aheart 101. With respect to the heart 101, the autoretroperfusion system100 may be used for treatment of myocardial infarctions by injectingarterial blood into the coronary sinus in synchronism with the patient'sheartbeat. Furthermore, the autoretroperfusion system 100 is capable ofcontrolling the pressure of the arterial blood flow as it enters thevenous vessel such that when the arterial blood flow is first introducedinto the venous system, the pressure of the re-routed arterial bloodflow is reduced to protect the thinner venous vessels. In this manner,the venous system is allowed to gradually arterialize. Further, afterthe selected venous vessel has sufficiently arterialized, theautoretroperfusion system 100 is capable of reducing or ceasing itsinfluence on the pressure of the re-routed arterial blood flow such thatthe standard arterial blood flow pressure is thereafter allowed to flowinto the arterialized venous vessel.

Autoretroperfusion system 100 comprises the catheter 10, a secondcatheter 150, and a connector 170. The catheter 10 is for placementwithin an arterial vessel and is configured as previously described inconnection with FIGS. 1-2B. The second catheter 150 is configured forplacement within the venous system. The connector 170 is configured toform an anastomosis between the catheter 10 and the second catheter 150and further functions to monitor various data points on the blood flowflowing therethrough. In addition, in at least one embodiment, theconnector 170 is capable of controlling the pressure of arterial bloodflowing therethrough.

The second catheter 150 is configured for placement within a venousvessel wall 114 and comprises a flexible tube having a proximal end 152,a distal end 154 and at least one lumen 156 extending between theproximal end 152 and the distal end 154. Both the proximal end 152 andthe distal end 154 of the second catheter 150 are open and incommunication with the at least one lumen 156 of the second catheter150, thereby allowing blood to flow into the at least one lumen 156through the proximal end 152 and out of the distal end 154 back into thevenous vessel 114. The second catheter 150 may be any catheter known inthe art that is capable of intravascular insertion and advancementthrough the venous system and may comprise any appropriate material,including without limitation, polyurethane or silicone rubber. In atleast one embodiment, the second catheter 150 is configured to receive aguidewire 510 (see FIGS. 4A and 4B) through the at least one lumen 156to facilitate the intravascular delivery of the distal end 154 of thesecond catheter 150 into the desired location of the venous vessel 114.Furthermore, similar to the catheter 10, the second catheter 150 may becoated with heparin or any other suitable anti-coagulant prior toinsertion in order to facilitate the extended placement of the secondcatheter 150 within the venous vessel 114. Accordingly, theautoretroperfusion system 100 may be used to deliver chronicretroperfusion treatment to an ischemic area of a body.

FIGS. 4A and 4B show side views of the distal end 154 of the secondcatheter 150 positioned within the venous vessel wall 114. As shown inFIG. 4A, the distal end 154 of the second catheter 150 may furthercomprise an expandable balloon 158 coupled with the external surface ofthe second catheter 150. In operation, the expandable balloon 158 can beused to anchor the distal end 154 of the second catheter 150 in thedesired location within the venous vessel wall 114. The expandableballoon 158 may be any expandable balloon that is appropriate forinsertion within a vessel and can be formed of any material suitable forthis function, including without limitation, polyethylene, latex,polyestherurethane, polyurethane, sylastic, silicone rubber, orcombinations thereof.

The expandable balloon 158 is capable of being controlled by a cliniciansuch that it can inflate and/or deflate to the proper size. The sizingof the expandable balloon 158 will differ between patients andapplications and it is often important to determine the proper sizing ofthe expandable balloon 158 to ensure the distal end 154 of the secondcatheter 150 is securely anchored within the desired location of thevessel wall 114. The accurate size of the expandable balloon 158 can bedetermined through any technique known in the art, including withoutlimitation, by measuring the compliance of the expandable balloon 158 exvivo or in vivo. In addition, the distal end 154 of the second catheter150 may further comprise a plurality of electrodes that are capable ofaccurately measuring the cross-sectional area of the vessel of interestas is known in the art. For example, the plurality of electrodes maycomprise a combination of excitation and detection electrodes asdescribed in detail in the currently pending U.S. patent applicationSer. No. 11/891,981 entitled System and Method for MeasuringCross-Sectional Areas and Pressure Gradients in Luminal Organs, andfiled on Aug. 14, 2007, which is hereby incorporated by reference in itsentirety. In at least one embodiment, such electrodes may compriseimpedence and conductance electrodes and may be used in connection withports for the suction of fluid from the vessel and/or the infusion offluid therein.

The expandable balloon 158 may be in fluid communication with asecondary lumen 160 disposed within the at least one lumen 156 of thesecond catheter 150. In this example, the secondary lumen 160 is coupledwith a balloon port 162 that extends from the proximal end 152 of thesecond catheter 150 (see FIG. 3). Accordingly, when theautoretroperfusion system 100 is positioned within a patient, theballoon port 162 can be easily accessed by a clinician, subcutaneously,percutaneously or otherwise, and used to inflate or deflate theexpandable balloon 158 with no or minimal invasion to the patient.

As shown in FIGS. 4A and 4B, the distal end 154 of the second catheter150 may further comprise at least one sensor 166 coupled therewith. Inat least one embodiment, the at least one sensor 166 is disposed on thedistal end 154 of the second catheter 150 distally of the expandableballoon 158; however, it will be understood that the at least one sensor166 may be disposed in any location on the distal end 154 of the secondcatheter 150.

The at least one sensor 166 may be used for monitoring purposes and, forexample, may be capable of periodically or continuously monitoring thepressure of the blood flow flowing through the at least one lumen 156 ofthe first catheter 150 or the venous vessel 14 in which the secondcatheter 150 is inserted. Additionally, one of the at least one sensors166 may be used to monitor the pH or the concentrations of carbondioxide, lactate, or cardiac enzymes within the blood. Furthermore, theat least one sensor 166 is capable of wirelessly communicating theinformation it has gathered to a remote module through the use oftelemetry technology, the internet, or other wireless means, such thatthe information can be easily accessed by a clinician on a real-timebasis or otherwise.

Now referring back to FIG. 3, the autoretroperfusion system 100 furthercomprises a connector 170. The connector 170 comprises any connector orquick connector known in the medical arts that is capable of forming ananastomosis between an artery and a vein such that oxygenated blood fromthe arterial system can flow into the venous system. For example, theconnector 170 may comprise an annular connector that is capable ofcoupling with the proximal end 20 of the projection cannula 16 of thecatheter 10 and with the proximal end 152 of the second catheter 150such that arterial blood can flow continuously from the at least onelumen 15 of the catheter 10 to the at least one lumen 156 of the secondcatheter 150. The connector 170 may be formed of any suitable materialknown in the art including, but not limited to, silicon rubber,poly(tetrafluoroethene), and/or polyurethane.

The connector 170 of the autoretroperfusion system 100 may comprise apressure/flow regulator unit that is capable of measuring the flow rateof the blood moving therethrough, the pressure of the blood movingtherethrough, and/or other data regarding the blood flowing through theanastomosis. The connector 170 may also be capable of transmitting suchgathered data to a remote module 180 through a lead placedintravascularly or, in the alternative, through telemetry or anotherwireless means. The remote module 180 may comprise any device capable ofreceiving the data collected by the connector 170 and displaying thesame. For example, and without limitation, the remote module 180 maycomprise any display device known in the art or a computer, amicroprocessor, hand-held computing device or other processing means.

Additionally, the connector 170 may further comprise a means forregulating the blood flow through the anastomosis. One of the mainchallenges of successfully delivering retroperfusion therapies is thatthe arterial blood pressure must be reduced prior to being introducedinto a vein due to the thinner and more fragile anatomy of venous walls.Indeed, subjecting a non-arterialized venous vessel to the highpressures of arterial blood flow typically results in rupture of thevenous vessel. Accordingly, with retroperfusion therapies, it iscritical to ensure that the pressure of the arterial blood flow is atleast initially controlled such that the venous vessel can arterializeprior to being subjected to the unregulated pressure of the arterialblood flow.

In at least one embodiment the connector 170 may comprise an externalcompression device to facilitate the control of the flow rate of theblood moving through the anastomosis. Alternatively, other means thatare known in the art may be employed to regulate the blood flow andpressure of the blood flowing through the anastomosis formed by theconnector 170. In at least one embodiment, the means for regulating theblood flow through the anastomosis formed by the connector 170 iscapable of regulating the pressure and/or flow velocity of the bloodflowing through the anastomosis. For example, the means for regulatingblood flow can be adjusted to ensure that about a 50 mg Hg pressure dropoccurs in the blood flow between the arterial vessel and the venousvessel.

The connector 170 is capable of not only transmitting data to the remotemodule 180, but also receiving commands from the remote module 180 andadjusting the means for regulating blood flow pursuant to such commands.Accordingly, when the autoretroperfusion system 100 is positioned withina patient for retroperfusion therapy, a clinician can use the remotemodule 180 to view the blood flow data collected by the connector 170and non-invasively adjust the connector 170 to achieve the desiredpressure and/or flow through the anastomosis. Such remote control of theconnector 170 is particularly useful as a clinician may incrementallydecrease the connector's 170 regulation of the blood flow withoutsurgical intervention during the venous arterialization process and/orafter the venous vessel arterializes.

Further, where the remote module 180 comprises a computer or otherprocessing means, the remote module 180 is also capable of beingprogrammed to automatically analyze the data received from the connector170 and, based on the results thereof, suggest how to adjust the meansof regulating the blood flow of the connector 170 and/or automaticallyadjust the means of regulating the blood flow of the connector 170 toachieve the optimal result. For example, and without limitation, whenthe autoretroperfusion system 100 is implanted into a patient and theanastomosis is first performed, the remote module 180 can automaticallyadjust the means for regulating the blood flow of the connector 170based on the initial blood flow data received by the remote module 180.In this manner, the desired pressure drop between the arterial systemand the venous system is immediately achieved and the risk of venousrupture is significantly reduced.

Alternatively, where the connector 170 of the autoretroperfusion system100 does not comprise a means for regulating blood flow, the gradualarterialization of the venous vessel can be achieved through othertechniques known in the art. For example, in at least one embodiment,the autoretroperfusion system 100 further comprises a coil designed toat least partially occlude the vein of interest. In this manner, thepressure is allowed to build in front of the portion of the vein atleast partially occluded by the coil and the vein graduallyarterializes. In this at least one embodiment, the coil may comprise ametallic memory coil (made of nitinol, stainless steel or otheracceptable materials that are radioopaque) and is covered withpolytetrafluorethylene, polyethylene terephthalate, polyurethane or anyother protective covering available in the medical arts.

Additionally, gradual arterialization can be performed by the secondcatheter 150. In this embodiment of autoretroperfusion system 100, theat least one lumen 156 of the second catheter 150 is designed to providean optimal stenosis geometry to facilitate the desired pressure drop asthe arterial blood flows therethrough and into the venous system. Forexample, and without limitation, the at least one lumen 156 may furthercomprise an internal balloon or resorbable stenosis as disclosed inInternational Patent Application No. PCT/US2006/029223, entitled“Devices and Methods for Controlling Blood Perfusion Pressure Using aRetrograde Cannula,” filed Jul. 28, 2006, which is hereby incorporatedby reference herein.

In at least one embodiment, the stenosis comprises an internalexpandable balloon (not shown) positioned within the lumen 156 of thesecond catheter 150. In this at least one embodiment, the internalexpandable balloon can be used to provide a pressure drop between thearterial and venous systems as is required to achieve the gradualarterialization of the target vein. The internal expandable balloon andthe external expandable balloon 158 of the second catheter 150 maypositioned concentrically or, alternatively, the internal expandableballoon and the expandable balloon 158 may be coupled with distinctportions of the second catheter 150.

The internal expandable balloon may comprise any material suitable inthe medical arts, including, without limitation, polyethylene, latex,polyestherurethane, polyurethane, sylastic, silicone rubber, orcombinations thereof. Further, the internal expandable balloon may be influid communication with a tertiary lumen (not shown) disposed withinthe at least one lumen 156 of the second catheter 150. In thisembodiment, the tertiary lumen is also in fluid communication with aninternal balloon port that extends from the proximal end 152 of thesecond catheter 150. Accordingly, the internal balloon port can beeasily accessed by a clinician, subcutaneously, percutaneously orotherwise, and the internal balloon port can be used to inflate ordeflate the internal expandable balloon with minimal or no discomfort tothe patient when the system 100 is in operation. Alternatively, theinternal expandable balloon may be in fluid communication with the atleast one lumen 156 of the second catheter 150. In this example, thearterial blood flow through the at least one lumen 156 functions toinflate and deflate the internal expandable balloon in conjunction withthe systolic and diastolic components of a heart beat.

The internal expandable balloon may be sized to a specific configurationin order to achieve the desired stenosis. In one embodiment, the size ofthe desired stenosis may be obtained by measuring the pressure at thetip of the distal end 156 of the second catheter 150 with the at leastone sensor 166 while the internal expandable balloon is being inflated.Once the desired intermediate pressure is obtained, the internalexpandable balloon volume may then be finalized and the vein isthereafter allowed to arterialize at the modified pressure for a definedperiod of time. At the end of the defined period (typically about 2-3weeks), the internal expandable balloon may be removed from the at leastone lumen 156 of the second catheter 150.

Insertion and/or removal of the internal expandable balloon from thesystem 100 may be achieved through the internal balloon port and therelated tertiary lumen of the second catheter 150. For example, if theinternal expandable balloon is no longer necessary to control thepressure on the venous system because the arterialization of the vein issubstantially complete, the internal expandable balloon can be deflatedthrough use of internal balloon port and withdrawn from the system 100through the tertiary lumen and the internal balloon port.

Other embodiments of the system 100 may comprise other suitable meansfor providing a stenosis within the at least one lumen 156 of the secondcatheter 150 such that a pressure drop is achieved in blood flowingtherethrough. For example, while a stenosis can be imposed by inflationof the internal expandable balloon, it may also be imposed throughpositioning a resorbable material within the at least one lumen 156 ofthe second catheter 150. The resorbable stenosis may be comprised of avariety of materials including, for example and without limitation,magnesium alloy and polyols such as mannitol, sorbitol and maltitol. Thedegradation rate of the resulting resorbable stenosis will be dependent,at least in part, upon on what type of material(s) is selected tomake-up the resorbable stenosis and the same may be manipulated toachieve the desired effect.

In addition to the aforementioned components of the autoretroperfusionsystem 100, the autoretroperfusion system 100 may further include afirst graft 185 and a second graft 190 as shown in FIG. 3. In thisembodiment, the first graft 185 is coupled with the proximal end 20 ofthe projection cannula 16 (that extends through the exterior arterialwall 116) and the connector 170. Further, the second graft 190 iscoupled with the proximal end 152 of the second catheter 150 (positionedwithin the venous vessel wall 114) and the connector 170. Accordingly,in this at least one embodiment, the second graft 190 is capable oftraversing the venous vessel wall 114 in such a manner that theanastomosis is sealed and no blood flow is allowed to leak from theanastomosed vein 114.

In this manner, the first and second grafts 185, 190 facilitate theformation of an elongated anastomosis between the venous and arterialvessels 114, 116 and thereby relieve any pressure that may be applied tothe two vessels 114, 116 due to the anastomosis formed therebetween. Forexample and without limitation, in at least one embodiment the combinedlength of the grafts 185, 190 and the connector 170 is about 6centimeters. However, it will be understood that the grafts 185, 190 maycomprise any length(s) so long as the dimensions allow for ananastomosis to form between the applicable vessels and a fully developedblood flow is achieved from the artery to the venous vessel of interest.

Alternatively, the autoretroperfusion system 100 may only comprise thesecond graft 190 in addition to the catheter 10, the second catheter 150and the connector 170. In this embodiment, the connector 170 is coupledwith the proximal end 20 of the projection cannula 16 and the secondgraft 190. Furthermore, the second graft 190 is further coupled with theproximal end 152 of the second catheter 150 such that the second graft190 traverses an opening within the venous vessel wall 114 (see FIG. 5).

The grafts 185, 190 may comprise any biocompatible, non-resorbablematerial having the necessary strength to support the surrounding tissueand withstand the pressure asserted by the blood flow therethrough.Furthermore, the grafts 185, 190 must exhibit the necessary flexibilityto form an anastomosis between the vein and the artery within which thecatheter 10 and the second catheter 150 are respectively housed. Forexample, and without limitation, the grafts 185, 190 may comprise anyconventional implant including synthetic and natural prosthesis, grafts,and the like. The grafts 185, 190 may also comprise a variety ofsuitable materials, including those conventionally used in anastomosisprocedures, including, without limitation, natural and syntheticmaterials such as heterologous tissue, homologous tissue, polymericmaterials, Dacron, fluoropolymers, and polyurethanes. For example, andwithout limitation, the first and second grafts 185, 190 may comprise amaterial such as GORE-TEX (polytetraflouroethylene). The grafts 185, 190may be coated with heparin or any other suitable anti-coagulant.Accordingly, the first graft 185 and the second graft 190 may be placedwithin a vessel or have blood flow therethrough for an extended periodof time without inhibiting blood flow due to coagulation.

In at least one embodiment of the autoretroperfusion system 100, thecomponents of the system 100 are available in a package. Here, thepackage may also contain at least one sterile syringe containing thefluid to be injected into the balloon port 62 to inflate the expandableballoon 58 of the catheter 10 and/or the balloon port 162 to inflate theexpandable balloon 158 of the second catheter 150. Furthermore, thepackage may also contain devices to facilitate delivery of theautoretroperfusion system 100 such as venous and arterial accessdevices, a delivery catheter, a guidewire and/or mandrel, an introducerto maintain the catheter 10 in the collapsed position during deliveryand, in those embodiments where a coil is used to arterialize the veinof interest, a pusher bar as is known in the art.

The guidewire used to facilitate the delivery of the autoretroperfusionsystem 100 into a vessel by providing support to the components thereof.The guidewire may comprise any guidewire known in the art. Furthermore,the distal end of the guidewire may comprise a plurality of impedanceelectrodes that are capable of taking measurements of the size thevessel in which the guidewire is inserted through the use of impedancetechnology. Additionally, in at least one embodiment, the impedanceelectrodes may be further capable of communicating such measurements tothe remote module 180 through telemetry or other wireless means in amanner similar to the at least one sensor 166 of the distal end 154 ofthe second catheter 150. In at least one embodiment, the distal end ofthe guidewire may comprise two tetrapolar sets of impedance electrodesdisposed on its distal-most tip.

Based on the information gathered by the impedance electrodes, aclinician can obtain accurate measurements of a selective region of avessel. In this manner, the expandable balloon 158 coupled with thedistal end 154 of the second catheter 150 may be properly sized and theamount of fluid or gas needed to inflate the expandable balloon 158 canbe determined prior to introducing the second catheter 150 into the veinof interest. For example, a clinician can use the plurality of impedanceelectrodes on the guidewire to obtain measurements of the size and shapeof the sub-branches of the coronary sinus. Details regarding thespecifications and use of the impedance electrodes are described indetail in the currently pending U.S. patent application Ser. No.10/782,149 entitled “System and Method for Measuring Cross-SectionalAreas and Pressure Gradients in Luminal Organs,” and filed on Feb. 19,2004, which is hereby incorporated by reference herein in its entirety.

Now referring to FIG. 5, components of a simultaneous selectiveautoretroperfusion system 300 are shown. The simultaneous selectiveautoretroperfusion system 300 (the “SSA system 300”) are configuredidentically to the autoretroperfusion system 100 except that the SSAsystem 300 further comprises a third catheter 350 and a Y connector 320,both configured for placement within the venous vessel wall 114.Specifically, the SSA system 300 comprises the catheter 10, the secondcatheter 150, the third catheter 350, the connector 170, and the Yconnector 320. It will be understood that the SSA system 300 can alsofurther comprise the first graft 185 and/or the second graft 190, andthe remote module 180 as described in connection with autoretroperfusionsystem 100.

The third catheter 350 is configured for placement within the venousvessel wall 114 adjacent to the second catheter 150. The third catheter350 is configured identically to the second catheter 150 and comprises aflexible tube having a proximal end 352, a distal end 354 and at leastone lumen 356 extending between the proximal end 352 and the distal end354. Both the proximal end 352 and the distal end 354 of the thirdcatheter 350 are open and in communication with the at least one lumen356 of the third catheter 350, thereby allowing blood to flow into theat least one lumen 356 through the proximal end 352 and out of thedistal end 354 back into the venous vessel 114.

The third catheter 350 may be any catheter known in the art that iscapable of intravascular insertion and advancement through the venoussystem. The third catheter 350 may comprise any appropriate material,including without limitation, polyurethane or silicone rubber. In atleast one embodiment, the third catheter 350 is configured to receive aguidewire 310 (see FIGS. 5 and 6) through the at least one lumen 356 inorder to facilitate the intravascular delivery of the distal end 354 ofthe third catheter 350 into the desired location of the venous vessel114. Furthermore, the third catheter 350 is coated with heparin or anyother suitable anti-coagulant prior to insertion in order to facilitatethe extended placement of the third catheter 350 within the venousvessel 114.

As shown in FIG. 5, the distal end 354 of the third catheter 350 furthercomprises an expandable balloon 358 coupled with the external surface ofthe third catheter 350. In operation, the expandable balloon 358 can beused to anchor the distal end 354 of the third catheter 350 in thedesired location within the venous vessel wall 114. The expandableballoon 358 may be any expandable balloon that is appropriate forinsertion within a vessel and can be formed of any material suitable forthis function, including without limitation, polyethylene, latex,polyestherurethane, polyurethane, sylastic, silicone rubber, orcombinations thereof.

Similar to the expandable balloon 158 of the second catheter 150, theexpandable balloon 358 is capable of being controlled by a cliniciansuch that it can inflate and/or deflate to the proper size. Theappropriate size of the expandable balloon 358 can be determined throughany technique known in the art, including without limitation, bymeasuring the compliance of the expandable balloon 358 ex vivo or invivo. Furthermore, when the guidewire 310 is used to facilitate thedelivery of the distal end 354 of the third catheter 350 into thedesired location within the venous vessel wall 114, the electrodes onthe distal end of the guidewire 310 may be used to accurately measurethe cross-sectional area of the venous vessel 114 such that theexpandable balloon 358 can be precisely sized prior to insertion intothe vein 114.

In this at least one embodiment, the expandable balloon 358 is in fluidcommunication with a secondary lumen 360 disposed within the at leastone lumen 356 of the third catheter 350. In this example, the secondarylumen 360 is coupled with a balloon port 362 that extends from theproximal end 352 of the third catheter 350. Accordingly, when the SSAsystem 300 is positioned within a patient, the balloon port 362 can beeasily accessed by a clinician, subcutaneously, percutaneously orotherwise, and used to inflate or deflate the expandable balloon 358with no or minimal invasion to the patient.

Similar to the second catheter 150, the distal end 354 of the thirdcatheter 350 may further comprise at least one sensor 366 coupledtherewith. The at least one sensor 366 may be configured identically tothe at least one sensor 166 of the second catheter 150 and, accordingly,the at least one sensor 366 may be used to monitor the pressure of bloodflow through the at least one lumen 356 of the third catheter 350 or thevenous vessel 114 or to monitor the pH or the concentrations of carbondioxide, lactate, or cardiac enzymes within the blood. Furthermore, theat least one sensor 366 is capable of communicating the data it gathersto the remote module 180 through the use of a wireless technology suchthat a clinician can easily access the gathered information on areal-time basis or otherwise. In at least one embodiment, the at leastone sensor 366 is disposed on the distal end 354 of the third catheter350 distally of the expandable balloon 358; however, it will beunderstood that the at least one sensor 366 may be disposed in anylocation on the distal end 354 of the third catheter 350.

The Y connector 320 of the SSA system 300 comprises flexible materialand has a proximal end 322, a distal end 324 and at least one lumen 326extending between the proximal and distal ends 322, 324. The proximalend 322 of the Y connector 322 is open and configured to be securelycoupled with the graft 190. The distal end 324 of the Y connector 322comprises two open ends which extend from the body of the Y connector322 in a substantially Y-shaped configuration. The two open ends of thedistal end 324 of the Y connector 322 thereby divide the at least onelumen 326 into two separate channels and thus the blood flowing throughthe at least one lumen 326 is yet again bifurcated.

The proximal end 152 of the second catheter 150 is coupled with one ofthe two open ends of the distal end 324 of the Y connector 322, therebyreceiving a portion of the blood flow that flows through the at leastone lumen 326 of the Y-connector. Similarly, the proximal end 352 of thethird catheter 350 is coupled with the other open end of the distal end324 of the Y connector 322 and, thus, the third catheter receives aportion of the blood flow that flows through the at least one lumen 326of the Y-connector. In this manner, the SSA system 300 can be used tosimultaneously retroperfuse more than one ischemic area of the body.

In application, the second catheter 150 and the third catheter 350 arepositioned adjacent to each other within the venous vessel wall 114 asshown in FIG. 5. Furthermore, the distal ends 154, 354 of the second andthird catheters 150, 350, respectively, may be placed within differentveins such that the arterial blood is delivered to selective portions ofischemic tissue. For example, as shown in FIG. 6, in at least oneembodiment the SSA system 300 can be applied to a heart 314 to providean arterial blood supply to two separate coronary veins, orsub-branches, simultaneously. In this at least one embodiment, thedistal ends 154, 354 of the second and third catheters 150, 350 are bothadvanced through the coronary sinus 370. As the diameter of the coronarysinus 370 ranges from about 10 to about 20 millimeters, cannulating thecoronary sinus 370 with both the second and third catheters 150, 350does not occlude the normal antegrade flow of the blood therethrough.Upon reaching the veins or sub-branches of interest, the distal ends154, 354 of the second and third catheters 150, 350 are eachindependently positioned within the veins of interest. In the exampleshown in FIG. 6, the second catheter 150 is positioned within theinterventricular vein 374 and the distal end 354 of the third catheter350 is positioned within the middle cardiac vein 376. As withautoretroperfusion system 100, the expandable balloons 158, 358 areinflated through balloon ports 162, 362, respectively (shown in FIG. 5),such that the distal ends 154, 354 of the second and third catheters150, 350 are securely anchored in the desired location within the veinsof interest. In this manner, the SSA system 300 can deliver controlledarterial blood flow to, and thus arterialize, two areas of the heart 314simultaneously.

In at least one embodiment of the SSA system 300, the components of thesystem 300 are available in a package. Here, the package may alsocontain sterile syringes with the fluids to be injected into the balloonports 162, 362 to inflate the expandable balloons 158, 358,respectively. Furthermore, the package may also contain devices tofacilitate delivery of the SSA system 300 such as arterial and venousaccess devices, a delivery catheter, at least two guidewires (configuredas described in connection with the delivery of autoretroperfusionsystem 100), an introducer to maintain the catheter 10 in the collapsedposition during delivery and, in those embodiments where a coil is usedto arterialize the vein of interest, a pusher bar as is known in theart.

Now referring to FIG. 7, a flow chart of a method 400 for performingautomatic retroperfusion using the system 100 is shown. While the method400 is described herein in connection with treating a heart throughcatheterization of the coronary sinus, it will be understood that themethod 400 may be used to perform autoretroperfusion on any organ ortissue in need of retroperfusion treatment and/or other areas near thecoronary sinus, such as the great cardiac vein, for example.

Method 400, and the embodiments thereof, can be performed under localanesthesia and do not require any arterial sutures. Further, onceimplanted, the system 100 can deliver chronic treatment to the patientas the system 100 is capable of remaining within a patient's vascularsystem for an extended period of time. In this manner, the system 100and method 400 can be used to treat no-option patients and greatlyenhance their quality of life.

As shown in FIG. 7, in one approach to the method 400, at step 402 anartery 502 of interest is percutaneously punctured under localanesthesia with a conventional artery access device or as otherwiseknown in the art. For example and without limitation, in at least oneembodiment, an 18 gauge needle is inserted into the femoral orsubclavian artery. At step 404, the catheter 10 housed in a collapsedposition within an introducer 504 (see FIG. 8A) is inserted into theartery 502 of interest. After the distal end 14 of the catheter 10 ispositioned in the desired location within the artery 502, the introducer504 is proximally withdrawn from the artery 502 as shown in FIG. 8B,leaving the catheter 10 positioned therein.

In at least one embodiment, the projection cannula 16 is configured suchthat when the introducer 504 is withdrawn in a proximal direction, theproximal end 12 of the catheter 10 is released from the introducer 504before the proximal end 20 of the projection cannula 16 is released fromthe introducer 504. In this manner, the proximal end 12 of the catheter10 is delivered within the interior of the arterial wall 502, while theprojection cannula 16 remains housed within the interior of theintroducer 504 as shown in FIG. 8C. Furthermore, because the introducer504 no longer applies downward pressure to the projection cannula 16relative to the proximal end 12 of the catheter 10, the projectioncannula 16 is allowed to shift from the collapsed position to theexpanded position and therefore extends in a direction that is notparallel with the artery 502 or the body of the catheter 10. In thismanner, as shown in FIGS. 8C and 8D, the proximal end 20 of theprojection cannula 16 is directed through the opening formed in thearterial wall 502 by the introducer 504.

Accordingly, when the catheter 10 is positioned within the artery 502,the antegrade blood arterial blood flow is allowed to continue throughthe artery 502 through the proximal end 12 of the catheter 10, whileonly a portion of the arterial blood is rerouted through the projectioncannula 16 and into the veins 506 of interest. In this manner, thenormal blood flow through the artery 502 is not inhibited by operationof the autoretroperfusion system 100. Furthermore, in addition tobifurcating the blood flowing through the artery 502, the projectioncannula 16 traversing the arterial wall 502 further functions to anchorthe catheter 10 in the desired position within the artery 502.

In the embodiment where the catheter 10 further comprises the expandableballoon 58 (see FIG. 1), step 404 may further comprise inflating theexpandable balloon 58 to the desired size by injecting fluid into theballoon port 62. In this manner, the expandable balloon 58 functions tofurther anchor the catheter 10 in the desired location within the artery502 and seal the opening in the artery 502 through which the projectioncannula 16 projects (see FIG. 8E).

At step 406, a vein 506 of interest is percutaneously punctured underlocal anesthesia with a conventional venous access device or asotherwise known in the art. For example and without limitation, in atleast one embodiment, an 18 gauge needle is inserted into the femoral orsubclavian vein. At step 408, a delivery catheter 508 is inserted intoand advanced through the vein 506 to catheterize the coronary sinusostium. A guidewire 510 is then inserted at step 410 into the deliverycatheter 510 and advanced into the lumen of the vein 506 through thedistal end of the delivery catheter 510. Furthermore, the guidewire 510is advanced into the region of interest by use of x-ray (i.e.fluoroscopy), direct vision, transesophageal echocardiogram, or othersuitable means or visualization techniques.

FIGS. 9 and 10 show schematic views of the method 400 as applied to aheart 500. Specifically, in this at least one embodiment, at steps 402and 404 the artery 502, which in FIG. 9 comprises the subclavian artery,is punctured and the catheter 10 is inserted and positioned therein.Further, at step 406 the vein 506, which in FIG. 9 comprises thesubclavian vein, is punctured and at step 408 the delivery catheter 508is advanced through the superior vena cava 518 and into the coronaryostium of the coronary sinus 520. As shown in FIG. 10, at step 410, theguidewire 510 is advanced through the coronary sinus 520 and into thevein of interest, which, in this at least one embodiment, comprises theposterior vein 522 of the heart 500.

Now referring back to FIG. 7, the guidewire 510 inserted into the vein506 at step 410 may further comprise a plurality of impedance electrodesas previously described herein. In this approach, the guidewire 510 maybe used at optional step 411 to determine the size of the vessel ofinterest through use of the plurality of impedance electrodes disposedthereon. In this manner, a clinician can use the measurements generatedby the impedance electrodes to select a properly sized expandableballoon 158 for use in connection with the second catheter 150. By usinga precisely sized expandable balloon 158 and inflation volume, theclinician can ensure that the distal end 154 of the second catheter 150is securely anchored within the vessel of interest without imposing anundue force on the venous vessel walls.

After the guidewire 510 has been advanced into the vessel of interest atstep 410 and, optionally, the dimensions of the vessel of interest havebeen measured at step 411, the method 400 advances to step 412. At step412, the distal end 154 of the second catheter 150 is inserted into thedelivery catheter 508 over the guidewire 510. Accordingly, the guidewire510 is slidably received by the at least one lumen 156 of the secondcatheter 150. The distal end 154 of the second catheter 150 is thenadvanced over the guidewire 510 to the region of interest and theexpandable balloon 158 of the second catheter 150 is inflated to anchorthe distal end 154 within the targeted vessel. FIG. 11 shows a schematicview of the method 400, as applied to the heart 500, after step 412 hasbeen completed. It will be understood that at any point after the distalend 154 of the second catheter 150 is positioned and anchored within thedesired location in the targeted vessel, the delivery catheter 508 andthe guidewire 510 may be withdrawn from the vein of interest.

After the distal end 154 of the second catheter 150 is secured withinthe targeted vessel, at step 414 the anastomosis between the vein 506and the artery 502 is formed. Specifically, in at least one approach,the proximal end 20 of the projection cannula 16 of the catheter 10 iscoupled with the proximal end 152 of the second catheter 150 by way ofthe connector 170. In the at least one embodiment of the system 100comprising the first graft 185 and the second graft 190, the connector170 may be coupled with the catheter 10 and the second catheter 150 viathe first graft 185 and the second graft 190 to form an elongatedanastomosis. Alternatively, in yet another approach, the connector 185may be coupled with the catheter 10 via the proximal end 20 of theprojection cannula 16 and the second catheter 150 via only the secondgraft 190. It will be understood that any combination of the catheter10, the second catheter 150 and the first and second grafts 185, 190 maybe used in connection with the connector 170 to form the desiredanastomosis between the vein 506 and the artery 502.

After the anastomosis is formed and the arterial blood is allowed toflow through the anastomosis and thereby through the connector 170, atstep 416 the connector 170 measures the flow rate, pressure and anyother desired data of the arterial blood flow. The connector 170transmits the collected data to the remote module 180 either throughintravascularly placed leads or wirelessly, through telemetry or othermeans. In this manner, a clinician may easily view the blood flow dataon the remote module 180 and assess the degree of pressure drop thatwill be required to preserve and gradually arterialize the vein 506.

At step 418, the pressure of the arterial blood flow through the system100 is modified to transmit the desired pressure to the venous system.In this step 418 the pressure modification can be achieved through aclinician modifying the means of regulating the blood flow of theconnector 170 through remote means or, in at least one embodiment of thesystem 100, inflating the internal expandable balloon of the secondcatheter 150 using the internal balloon port in order to partiallyocclude the flow of arterial blood through the at least one lumen 156 ofthe second catheter 150. Furthermore, in at least one alternativeembodiment of the system 100, a clinician may deliver a resorbablestenosis configured to achieve the necessary pressure drop into the atleast one lumen 156 of the second catheter 150 through means known inthe art.

Alternatively, as previously described in connection withautoretroperfusion system 100, the remote module 180 may furthercomprise a computer or other processing means capable of beingprogrammed to automatically analyze the data received from the connector170 and, based on such data, determine the proper degree of adjustmentrequired in the blood pressure flowing through the anastomosis. In thisembodiment, at step 418, the remote module 180 automatically adjusts themeans of regulating the blood flow of the connector 170 to achieve theoptimal pressure drop. In this manner, the desired pressure drop betweenthe arterial system and the venous system is immediately achieved andthe risk of venous rupture is significantly reduced.

In step 420 the method 400 allows the arterial blood having a modifiedpressure to irrigate the vein 506 for a period of time such that thevein 506 properly arterializes. For example, and without limitation, thepatient's venous system may be subjected to the reduced arterialpressure for about fourteen days to allow the vein 506 to adapt to theelevated blood pressure flowing therethrough.

After arterialization of the vein 506 is achieved, at step 422 thepatient may optionally undergo a coronary venous bypass graft surgeryand the components of the autoretroperfusion system 100 may be removed.However, as previously discussed, even with a properly arterialized vein506, many patients that require retroperfusion therapy may still not becandidates for a coronary vein bypass graft surgery. In the event thatthe patient is unable to tolerate such a procedure, after the vein 506has arterialized at step 420, the method 400 can progress directly tostep 424. At step 424, the pressure modification of the arterial bloodflowing through the second catheter 150 is ceased. Accordingly,pre-arterialized veins 506 are subjected to the full arterial pressureof the blood flowing through the anastomosis and second catheter 150. Inat least one embodiment, a clinician can cease the pressure modificationby adjusting the controller 170. Alternatively, in the at least oneembodiment where the controller 170 can be automatically adjusted by theremote module 180, the remote module 180 can automatically adjust thecontroller 170 after the veins 506 have pre-arterialized. Further, wherethe pressure drop is achieved through the use of an internal expandableballoon positioned within the at least one lumen 156 of the secondcatheter, the clinician may deflate the internal expandable balloonthrough the internal balloon port and thereafter withdraw the deflatedinternal expandable balloon through the tertiary lumen of the secondcatheter and the internal balloon port. In yet another embodiment wherea resorbable stenosis is used to achieve the pressure drop in thearterial blood as it flows through the second catheter 150, theresorbable stenosis can be configured to dissolve after the desiredperiod of time, thereby gradually decreasing the influence theresorbable stenosis has on the pressure of the blood flowing through theat least one lumen 156 of the second catheter over a period of time.Accordingly, the autoretroperfusion system 100 can remain chronicallyimplanted within the patient to deliver oxygen-rich blood to a targetedarea of tissue over an extended period of time.

Now referring to FIG. 12, a flow chart of a method 600 for performingsimultaneous selective retroperfusion using the SSA system 300 is shown.While the method 600 is described herein in connection with treating aheart 500 through catheterization of the coronary sinus 520, it will beunderstood that the method 600 may be used to perform autoretroperfusionon any organ or tissue in need of retroperfusion treatment. Thereference numerals used to identify the steps of method 600 that areincluded in the description of method 400 designate like steps betweenthe two methods 400, 600. As such, like steps between the two methods400, 600 will not be discussed in detail with respect to the method 600and it will be understood that such description can be obtained throughthe description of the method 400.

Method 600, and the embodiments thereof, can be performed under localanesthesia and does not require arterial sutures. Further, onceimplanted, the SSA system 300 can deliver simultaneous chronic treatmentto multiple ischemic locations as the system 300 is capable of remainingwithin a patient's vascular system for an extended period of time andselectively retroperfusion more than one sub-branch of a vein 506.

The method 600 progresses through steps 402 through 410 as previouslydescribed in connection with the method 400. After the guidewire 510 isadvanced through the coronary sinus 520 and into the first vein ofinterest, a second guidewire 610 is inserted at step 602 into thedelivery catheter 508 adjacent to the guidewire 510, and advanced intothe lumen of the vein 506 through the distal end of the deliverycatheter 510. The second guidewire 610 is then advanced into a secondregion of interest by use of x-ray (i.e. fluoroscopy), direct vision,transesophageal echocardiogram, or other suitable means or visualizationtechniques. The second guidewire 610 is configured similar to theguidewire 510 and is capable of functioning the in the same manner.

FIG. 13 shows a schematic view of the method 600 as applied to a heart500. Specifically, in this at least one embodiment, FIG. 13 shows themethod 600 at step 602 wherein the guidewire 510 is inserted a firstvein of interest, which comprises the posterior vein 522 of the heart500, and the second guidewire 610 is inserted into a second vein ofinterest, which comprises the interventricular vein 622 of the heart500.

Now referring back to FIG. 12, the guidewire 610 inserted into thesecond vein of interest in step 602 may further comprise a plurality ofimpedance electrodes as previously described with respect to theguidewire 510. In this embodiment, the guidewire 610 may be used atoptional step 603 to determine the size of the second vessel of interestthrough use of the plurality of impedance electrodes disposed thereon.In this manner, a clinician can use the measurements generated by theimpedance electrodes to select a properly sized expandable balloon 358for use in connection with the third catheter 350. By using a preciselysized expandable balloon 358 and inflation volume, a clinician canensure that the distal end 354 of the third catheter 350 is securelyanchored within the second vessel of interest without imposing an undueforce on the venous vessel walls.

After the guidewire 610 has been advanced into the second vessel ofinterest at step 602 and, optionally, the dimensions of the secondvessel of interest have been measured at step 603, the method 600advances to step 412 wherein the second catheter 150 is inserted overthe guidewire 510 as described in connection with method 400. At step604, the distal end 354 of the third catheter 350 is inserted into thedelivery catheter 508 over the second guidewire 610. Accordingly, thesecond guidewire 610 is slidably received by the at least one lumen 356of the third catheter 350. The distal end 354 of the third catheter 350is then advanced over the second guidewire 610 to the second region ofinterest and the expandable balloon 358 of the third catheter 350 isinflated to anchor the distal end 354 within the targeted vessel. FIG.14 shows a schematic view of the method 600 at step 604 as applied tothe heart 500. It will be understood that at any point after the distalends 154, 354 of the second and third catheters 150, 350 are positionedand anchored in the desired locations within the targeted vessels, thedelivery catheter 508 and the guidewires 510, 610 may be withdrawn fromthe vein 506.

After both the distal end 154 of the second catheter 150 and the distalend 354 of the third catheter 350 are secured within the targetedvessels, the method 600 proceeds to step 414 where the anastomosis isformed between the vein 506 and the artery 502 as described inconnection with method 400. Thereafter, the method 600 advances throughsteps 416 through 424 as described in connection with the method 400.Furthermore, at step 418, it will be recognized that a clinician canindependently adjust the pressure drop through the second and thirdcatheters 150, 350 in the event that an internal expandable balloon isused in either or both catheters 150, 350 or resorbable stenosis areemployed within the at least one lumens 156, 356 of the second and thirdcatheters 150, 350. Alternatively, in the at least one embodiment wherethe controller 170 comprises a means for regulating the blood flowthrough the anastomosis, the pressure of the arterial blood flowingthrough both the second and third catheters 150, 350 may besubstantially the same.

As described herein, the method 600 may be used to simultaneously andimmediately treat two different ischemic areas of a tissue through theuse of one minimally to non-invasive procedure. Furthermore, the method600 can provide no-option patients with a viable treatment option thatis not associated with contraindications for congestive heart failure,diabetes, or drug treatment.

An additional embodiment of a perfusion system 100 of the presentdisclosure is shown in FIG. 15. As shown in FIG. 15, system 100comprises a first catheter 1000 having a distal end 1002, a proximal end1004, and defining a lumen 1006 therethrough, wherein at least a portionof first catheter 1000 is configured for insertion into a body of apatient, such as into a patient's heart or a patient's vein, forexample. First catheter 1000, after insertion into a patient's vein orheart, for example, is capable of providing arterial blood (which isrelatively rich in oxygen and other nutrients) thereto by way oftransfer of arterial blood from, for example, a patient's artery, asdescribed below, into a proximal catheter opening 1008, through lumen1006, and out of distal catheter opening 1010. In such a fashion, forexample, a system 100 can be referred to as an autoretroperfusion system100, noting that no outside pumps are necessary (as the patient's ownheart serves as the pump), and due to the retrograde nature of theperfusion with respect to such a use. Exemplary uses, as provided indetail herein, are to provide arterial blood, using system 100, to apatient's femoral vein, internal jugular vein, subclavian vein, and/orbrachial cephalic vein. In an exemplary embodiment, first catheter 1000may be tapered toward distal end 1002 to facilitate insertion into apatient.

In at least one embodiment of system 100, and as shown in FIGS. 15 and16, system 100 comprises a coupler 1012 having an outlet port 1013 andone or more additional ports to facilitate connection outside of thepatient's body. For example, and as shown in FIGS. 15 and 16, coupler1012 comprises an inflation port 1014, whereby fluid and/or gasintroduced into inflation port 1014 can be used to inflate an expandableballoon 1016 positioned along first catheter 1000 at or near the distalend 1004 of first catheter 1000. As shown in the figures, and in atleast one embodiment, an inflation tube 1018 may be coupled to inflationport 1014 at a distal end 1020 of inflation tube 1018, whereby inflationtube 1018 may also have an optional flow regulator 1022 positionedrelative thereto to regulate the flow and/or pressure of fluid and/orgas in and out of a lumen 1024 of inflation tube 1018 to inflate anddeflate expandable balloon 1016. Inflation tube 1018 may furthercomprise a proximal connector 1026 configured to receive fluid and/orgas from a fluid/gas source (not shown), whereby proximal connector 1026can be positioned at or near a proximal end 1028 of inflation tube 1018,for example. Inflation of expandable balloon 1016, for example, can beused to anchor first catheter 1000 to a desired position within aluminal organ of a patient.

An exemplary coupler 1012 of the present disclosure further comprises anarterial blood port 1030 configured to receive arterial/oxygenated bloodfrom, for example, an arterial blood tube 1032 coupled thereto at ornear a distal end 1034 of arterial blood tube 1032. As shown in FIGS. 15and 16, a blood flow regulator 1036 may be positioned relative toarterial blood tube 1032 and operate to regulate the flow and/orpressure of arterial/oxygenated blood flow therethrough. In at least oneembodiment, blood flow regulator 1036 comprises a rotatable dial capableof rotation to apply and/or remove pressure to/from arterial blood tube1032 to regulate the flow and/or pressure of blood through a lumen 1038of arterial blood tube 1032 and/or to adjust pressure therein based uponidentified blood pressure measurements. Such a blood flow regulator1036, for example, can be used to control blood pressure to limit injuryto the patient's luminal organs (such as the patient's venous systemand/or myocardium) and/or to minimize potential edema with respect tothe same luminal organs. Arterial blood tube 1032 may further comprise aproximal connector 1040 configured to receive arterial/oxygenated bloodfrom a blood supply, whereby proximal connector can be positioned at ornear a proximal end 1040 of arterial blood tube 1032, for example. Acoupler catheter 1042, as shown in the component block diagram of system100 shown in FIG. 17, may be used to couple arterial blood tube 1032 toa blood supply 1044, which, as described herein, could be a patient'sown artery using the patient's heart as a pump, or could be an externalsupply that provides blood to arterial blood tube 1032, which may thenbe used in connection with an apparatus to remove blood from the patientas well.

Furthermore, and in at least one embodiment, an exemplary coupler 1012of the present disclosure further comprises a medicament port 1046configured to receive a medicament, saline, and/or the like, so that thesame can enter the patient by way of first catheter 1000. Medicamentport 1046, as shown in FIGS. 15 and 16, may receive a medicament tube1048 defining a lumen 1050 therethrough, whereby a distal end 1052 ofmedicament tube 1048 can couple to medicament port 1046 so that amedicament, saline, and/or the like can be introduced from a medicamentsource (not shown) coupled to medicament tube 1052 at or near a proximalend 1054 of medicament tube 1048. Exemplary medicaments may include, butare not limited to, fibrinolitic drugs, cardiotonic drugs, antirrhytmicdrugs, scavengers, cells or angiogenic growth factors, for example,through the coronary vein or another luminal organ. In at least oneembodiment, and as shown in FIGS. 15 and 16, medicament tube 1048 can bebranched, whereby a second proximal end 1056 of medicament tube 1048 canreceive a medicament and control the flow of medicament therethrough,for example, by way of a medicament regulator 1058 positioned relativeto medicament tube 1048, for example. Furthermore, one or more ofproximal end 1054 and second proximal end 1056 may be configured toreceive a wire therein, such as, for example, a 0.035″ guidewire and/ora 0.014″ pressure wire. As generally referenced herein, any blood, air,fluid, medicament, wire, etc. that enters coupler 1012 by way ofinflation port 1014, arterial blood port 1030, and/or medicament port1046 and eventually enters a lumen of first catheter 1000 will enter oneor more of said ports of coupler 1012 and exit outlet port 1013 at thetime of entry into first catheter 1000.

FIG. 17, as referenced above, is a block diagram of various componentsof an exemplary system 100 of the present disclosure. As shown therein,an exemplary embodiment of a system 100 of the present disclosurecomprises a first catheter 1000, a coupler 1012, an arterial blood tube1032 with a blood flow regulator 1036, and a coupler catheter 1042configured to for connection to a blood supply 1044, wherein the bloodsupply may or may not be considered as part of a formal system 100. Inaddition, an exemplary system 100 may comprise an inflation tube 1018with a flow regulator 1022, whereby an end of inflation tube 1018 isconfigured for connection to a gas/liquid source 1060. Variousembodiments of systems 100 of the present disclosure may have more orless components than shown in FIG. 17, and exemplary embodiments ofsystems 100 of the present disclosure may be configured to engagevarious embodiments of catheters 10 as referenced herein.

In use, for example, first catheter 1000 of system 100 may be positionedwithin a luminal organ of a patient within the patient's venous system.Inflation of expandable balloon 1016 to secure first catheter 1000 cannot only provide oxygenated arterial blood to the patient's venoussystem, but can also continue to allow coronary venous return tocontinue due to the selective autoretroperfusion nature of an exemplaryembodiment of system 100 and use thereof and due to the redundancy ofthe patient's venous system. In the event that an increased pressure,edema, or other undesired condition may occur at or near the site ofinflated expandable balloon 1016, a user of system 100 could, ifdesired, temporarily deflate expandable balloon 1016 to allow theincreased pressure and or edema to alleviate itself. For example, system100 could be used for a relatively long period of time (an hour, by wayof example), and expandable balloon 1016 could be deflated for arelatively short period of time (seconds, for example), to alleviate ahigh pressure or edema occurrence, and then expandable balloon 1016could be re-inflated to again secure first catheter 1000 at a desiredlocation within the patient.

The type of patients for whom the device will be utilized in the acuteapplication may fall into various categories, including, but not limitedto, S-T segment Elevated Myocardial Infarction (STEMI) patients,cardiogenic shock patients, and high risk Percutaneous CoronaryIntervention (PCI) patients (such as those undergoing PCI of the leftmain coronary artery). STEMI is the traditional “emergent” patient whopresents with classic heart attack symptoms, and when diagnosed in ahospital emergency room for example, the patient would traditionally beimmediately moved to a Cath Lab to receive PCI to open an occludedcoronary artery and restore blood flow to the myocardium. These patientsare hemodynamically unstable and need support for the left ventricle.

In such a use, for example, an exemplary system 100 of the presentdisclosure could be used to, for example:

(i) provide cardiac support to a patient who does not have immediateaccess to the Cath Lab and PCI. These patients may present in rural orcommunity hospitals that do not have Cath Labs. They will need some typeof temporary support while being transferred to an appropriate facility.These patients might also present at a hospital with a Cath Lab, but theCath Lab is either understaffed to treat the patient, or does not havean available room to treat. In these cases, the system 100 of thepresent disclosure operates as a bridge to provide support untildefinitive treatment (primary PCI) is available; and/or

(ii) provide cardiac support before, during, and after primary PCI. Manypatients enter the Cath Lab in an unstable condition, and the insertionof balloons and stents adds to hemodynamic instability. An exemplarysystem 100 can provide cardiac support and improve hemodynamics suchthat the physician can operate in a more stable/controlled environment.It is also believed that by reperfusing ischemic myocardiumbefore/during/and after primary PCI, one may reduce the amount ofmyocardium that is damaged by the ischemic event. This is clinicallyreferred to as a “reduction in infarct size.” Initial animal studies (asreferenced in further detail herein) have suggested that the use of SARPin support of STEMI patients could cause a reduction in infarct size,which would have a significant impact on the outcomes for the patient inboth the near and long term. Reduction in infarct size would slow theprogression of any subsequent heart failure and reduce long termhospitalization and costs for this group of patients.

Cardiogenic shock is marked by a significant lowering of blood pressureand cardiac output that if not reversed, will ultimately lead tomultisystem organ failure and death. Cardiogenic shock patients have amortality exceeding 60%. In many cases, cardiogenic shock patients aretoo unstable to undergo surgery or PCI. Pharmacologics are used toincrease pressure and cardiac output. Intra Aortic Balloon Pumps (IABP)and other LVAD type products are also employed to improve hemodynamicsin an attempt to reverse the downward cycle of cardiogenic shockpatients Exemplary embodiments of systems 100 of the present disclosurecould be used in much the same fashion.

High Risk PCI is typically defined as patients who have disease of theleft main coronary artery, are diabetic, have multivessel disease, areabove 75 years of age, have a prior history of MI, have renalinsufficiency, etc. These are very sick patients, who are considered athigh risk of adverse events before, during, and after undergoing PCI.Mortality rates and Major Adverse Cardiac Event (MACE) rates are muchhigher in this patient population. IABP's are commonly used in thispatient population.

In this population, systems 100 of the present disclosure may be used toprovide cardiac support for a high risk PCI patient who is, at the timeof the procedure, found to be hemodynamically unstable. It is evident tothe operator that cardiac support is and will be needed during theprocedure, and an exemplary system 100 of the present disclosure wouldbe deployed from the outset. The patient's hemodynamics improve and theoperator feels more comfortable working in the coronary system. IABP useis common in these patients.

Systems 100 of the present disclosure may also be used in this high riskpopulation when it is anticipated that cardiac support may be neededduring the procedure. In this case, an exemplary system 100 is deployedprior to the case, in order to provide support when and if it is needed.The patient is hemodynamically stable at the outset, and remains sothroughout. IABP's are currently used in this fashion. This is commonlyreferred to as prophylactic use of cardiac support.

Acute Applications: In this setting, exemplary systems 100 of thepresent disclosure will be used for cardiac support and to protectmyocardium for a period of time that will generally be less than 24hours. The clinical condition that precipitated the need for SARP willhave typically been resolved in that 24 hour period, and the system 100would be removed. However, use of systems 100 of the present disclosureare not limited to a 24 hour period, as in some cases, IABPs and othershort term cardiac support devices are left in for periods exceeding 24hours. Typically, the longest period of time that a short term devicemight be left in place is 4-6 days, at which point the clinician wouldbegin to consider longer term implanted Left Ventricular Assist Devices(LVADs), which can support a patient for an extended period of time(weeks), and are often used as a bridge to heart transplant.

Clinical conditions that would require the acute application of anexemplary system 100 of the present disclosure include, but are notlimited to:

(i) Emergent treatment of STEMI and/or other Acute Myocardial Infarction(AMI) patients;

(ii) Cardiogenic shock;

(iii) High Risk PCI;

(iv) Failed or aborted PCI where severe hemodynamic instability presentsafter initiation of the procedure. These patients are often transferredto immediate cardiac surgery, and require cardiac support while waitingfor the surgical intervention; and/or

(v) Weaning from a cardiopulmonary bypass machine in cardiac surgery.Some cardiac surgery patients have difficulty returning to normalcardiac condition when the cardiopulmonary bypass machine is turned offand the heart is restarted after successful revascularization in cardiacsurgery. Exemplary systems 100 of the present disclosure could be usedto support the heart until normal cardiac parameters return. Insertioncould occur in the surgical suite, and the device would be left in placewhile the patient was transferred to a Cardiac Critical Care Unit (CCU).

These exemplary clinical conditions cover the majority of potentialapplications for an acute embodiment of a system 100 of the presentdisclosure. Currently, more than 95% of all IABP and other short termsupport devices are used for these applications.

In such applications, the goal of using an exemplary system 100 of thepresent disclosure is to deliver arterial (oxygenated) blood to themyocardium, in a retrograde manner using the venous system, in order tocreate hemodynamic stability for the patient and to protect and preservemyocardial tissue until the clinical event resolves or primaryintervention (PCI or CABG) and revascularization can occur.

Chronic Applications: In this setting it is intended that an exemplaryembodiment of a system 100 of the present disclosure be implanted for 2weeks or longer, for example, noting that ultimate implantation may besomewhat shorter in duration. Initial animal studies suggest that within2 weeks, arterialization of the venous system is achieved, such that thevenous system can become the conduit for a constant flow of arterialblood at arterial pressure.

A clinical condition where the chronic application of a system 100 wouldbe utilized is often referred to as “no option” patients, that is,patients for which there are no options available through which theirclinical condition can be resolved. More specifically, these arepatients with diffuse coronary artery disease (CAD) or refractoryangina, where PCI and/or Coronary Artery Bypass Graft Surgery (CABG) isnot an option. Patients that are diabetic, or have other co-morbidities,and are not candidates for interventions, would be candidates for achronic application of a system 100 of the present disclosure.

As previously referenced herein, the chronic application will generallyrequire 10-14 days of retroperfusion in order to allow arterializationof the venous system. In certain instances, retroperfusion could berequired for a longer period (such as 2-3 weeks, for example), or alesser period, such as less than 10 days, for example. These patients,dependent upon their complete clinical situation, may be hospitalizedfor that period, or they may reside outside of the hospital. Whenresiding outside of the hospital, the device utilized may be a catheter10 embodiment with a branched implantable portion, such as shown in FIG.1, for example. The catheter 10, including method of pressureregulation, would be implanted in the patient.

For those chronic patients, who must remain in the hospital for one ofthe aforementioned time periods, an acute embodiment of a system 100,for example, may be applicable. In such an embodiment, for example,system 100 may be percutaneously inserted and utilized during that timeframe. Once arterialization occurs, a more permanent conduit may beconstructed percutaneously or surgically to provide the permanentarterial blood source.

When using an exemplary system 100 of the present disclosure, standardguide catheters can be used by the clinician to locate the coronarysinus and/or the great cardiac vein, for example. An 0.035″ guidewirecan be inserted to further establish access to the coronary sinus or thegreat cardiac vein. An exemplary system 100 can then be inserted overthe 0.035″ guidewire and advanced to the coronary sinus or the greatcardiac vein, for example, via one of the ports as referenced herein.

The distal end 1004 of the first catheter 1000 is intended to be locatedat the left main vein. The operator may advance the tip (distal end1014) of first catheter 1000 to other vein sites dependent on clinicalneed. A balloon 1016, which in at least one embodiment may be locatedapproximately 2 cm back from the distal end 1004, would then be inflatedto secure the position of first catheter 1000 within the coronary sinusor the great cardiac vein, for example, allowing for the distal end 1004of first catheter 1000 to locate at the left main vein. The inflatedballoon 1016 will also work to ensure that arterial blood will flow inthe retrograde fashion.

Once the distal balloon 1016 is inflated, the 0.035″ guidewire can beexchanged for an 0.014″ pressure measurement wire, which will be used tomeasure the pressure at the distal end 1004 of first catheter 1000, toensure that the portions of system 100 are not over pressurizing thevein, and to tell the operator how much pressure change will be requiredfrom the external pressure regulator. The proximal end of the pressurewire will be connected to its appropriate monitor.

When the catheter is located in the coronary sinus or the great cardiacvein, for example, the operator can now make the external (outside thebody) connection to the arterial blood supply 1044. This is typically,but not limited to, the femoral or radial arteries. The physician willhave previously inserted a standard procedural sheath into the arterialsource in order to gain access to the source. This arterial sheath canalso be used to provide access for catheters, guidewires, balloons,stents, or other devices that might be utilized while treating thepatient. That arterial sheath will have a connector which can connect tothe arterial supply cannula (with regulator) on the acute device (anembodiment of system 100). Once the connection is established and flowcommences, the pressure wire will indicate the distal pressuremeasurement and the regulator can be adjusted to the proper setting (notto exceed 60 mmhg, for example). Monitoring of the distal pressure willbe on-going throughout the period of time that the device is in-vivo.The regulator allows the operator to provide the correct distalpressures and to adjust those pressures, dependent on changes in thepatient's pressure.

With the pressure set and monitored, the patient is now receivingoxygenated blood to the myocardium in a retrograde fashion thru thecoronary venous system. Such an operation (namely to retrogradly provideoxygenated blood) can be used to save a significant amount of ischemictissue at the level of the border zone. In at least one embodiment, sucha system 100 is used to perfuse the left anterior descending vein tosupply oxygenated blood to the LAD artery occluded territory. Dependingupon patient need and circumstance, the acute device (an embodiment ofsystem 100) will be removed typically within the first 24 hours ofinsertion. The physician will make that determination. The insertionsite will be closed per hospital protocol.

Validation of Methodology

As referenced in detail herein, coronary artery disease (CAD) is thenumber one cause of morbidity and mortality in the U.S. and worldwide.Even today, with percutaneous transluminal coronary angioplasty (PTCA)and coronary artery bypass grafting (CABG), optimal and timely treatmentis still not available for all patients. Bridge therapies to complementexisting gold standards of reperfusion therapy would be of significantvalue to a large number of patients.

Because the coronary venous system rarely develops atherosclerosis, theuse of the venous system for delivery of oxygenated blood has been wellexplored. Synchronized retrograde perfusion (SRP) andpressure-controlled intermittent coronary sinus occlusion (PICSO) aretwo retroperfusion methods for acute treatment of myocardial ischemiathrough the coronary venous system. PICSO and SRP have been used inconjunction with a balloon-tipped catheter positioned just beyond theorifice of the coronary sinus connected to a pneumatic pump, and eitherpassively redirect coronary sinus blood (PICSO) or actively pumparterial blood during diastole (SRP) to the ischemic myocardium. Thesetechniques have been shown to decrease ischemic changes, infarct size,myocardial hemorrhage, and no-reflow phenomenon, and improve leftventricular (LV) function when coronary blood flow is reinstituted afteran acute occlusion. Wide application of these techniques, however, hasbeen limited by concerns over their safety and complexity, and inparticular, the need for repeated occlusion of the coronary sinus with aballoon. High pressure (SRP and PICSO) and flow (SRP) can cause damageto the coronary sinus with thrombosis and chronic myocardial edema.

We have validated in animal studies both the acute and chronicapplication of the methodologies referenced herein. In a recent acutestudy, we showed that preservation of the contractile function of theischemic myocardium can be accomplished with selectiveautoretroperfusion (SARP) without the use of an external pump duringacute LAD artery ligation. The hypothesis that SARP can preservemyocardial function at regulated pressures without hemorrhage of vesselsor damage of myocytes was verified. In connection with this animal work,a bolus of Heparin was given before instrumentation and was thensupplemented as needed to keep an activated clotting time (ACT) over 200seconds. The right femoral artery was cannulated with a 7Fr catheter andconnected to a pressure transducer (TSD104A—Biopac Systems, Inc) formonitoring of arterial pressure. Before the sternotomy, the rightcarotid artery was cannulated with a 10Fr polyethylene catheter througha ventrolateral incision on the neck to reach the brachiocephalic arteryto supply the LAD vein during retroperfusion. The catheter had a rollerclamp that was used to control the arterial pressure transmitted to theLAD vein. The right jugular vein was cannulated with an 8Fr catheter foradministration of drugs and fluids. Lidocaine hydrochloride was infusedat a rate of 60 μg/kg/min before opening the chest and during the restof the procedure. Magnesium sulfate (10 mg/min IV) along with lidocainwas also used to treat extrasystole in the case of the control group. Avasopressor (Levophed®, Norepinephrine Bitartrate Injection,Minneapolis, Minn., 2-6 μg/min IV) was used during the procedure, andwas adjusted accordingly to maintain a constant arterial blood pressure(70.0±8.9 mmHg, mean) in both the experimental and the control groups.Finally, heparin and nitroglycerine were diluted in 60 mL of 0.9% sodiumchloride and infused using a syringe pump at a rate of 1 ml/min. Thechest was opened through a midsternal thoracotomy, and an incision wasmade in the pericardium with the creation of a sling to support theheart with pericardial stay sutures.

A pair of piezoelectric ultrasonic crystals (2 mm in diameter on 34gauge copper wire—Sonometrics Corporation) were implanted through smallstab incisions in the anterior wall of the LV (area at risk) distal tothe planned site (below first diagonal branch in the SARP group, andsecond diagonal branch in the control group) of LAD artery ligation, forassessment of regional myocardial function through measurement ofmidwall segment length changes. An additional pair of crystals was alsoimplanted in the anterior wall of the LV within the normal perfusion bed(control area) of the proximal portion of the LAD artery.

FIG. 18 shows a schematic of the retroperfusion system showing thearterial and retroperfusion catheters. Each pair of crystals werepositioned in the midmyocardium (about 7 mm from the epicardium)approximately 10-15 mm apart and oriented parallel to the minor axis ofthe heart. The acoustical signal of the crystals was verified by anoscilloscope.

In the SARP group (ligation+retroperfusion) the LAD artery was dissectedfree from the surrounding tissue distal to the first diagonal branch forsubsequent ligation. A 2.5 mm flow probe was placed around the LADartery and connected to a flow meter (T403—Transonic Systems, Inc). TheLAD vein was also dissected close to the junction with the great cardiacvein, and the proximal portion ligated with 2-0 silk suture in order toprevent runoff to the coronary sinus. The LAD vein was then cannulatedbelow the ligation with a 10Fr cannula that was attached to thebrachiocephalic catheter through one of two four-way stopcocks. A flowprobe was placed between the stopcocks for measurement of coronaryvenous flow. Venous pressure was recorded through the pressuremonitoring line from the retroperfusion cannula (as shown in FIG. 18).Retroperfusion was initiated immediately after ligation of the LADartery and was maintained for a period of 3 hours. Arterial bloodsamples were taken at baseline and at the end of the first, second andthird hours of ligation+retroperfusion for monitoring of pH, hematocrit,electrolytes, activated clotting time, and cardiac troponin I.

Coronary venous SARP may be an effective method of protecting themyocardium during acute ischemia before definitive treatment isestablished as referenced herein regarding various catheter 10 andsystem 100 embodiments of the present disclosure. SARP may not onlyoffer protection to the ischemic myocardium through retrograde perfusionof oxygenated blood but may also serve as a route for administration ofthrombolytics, antiarrhythmics, and cell and gene therapy to thejeopardized myocardium before PTCA or CABG can be implemented inpatients eligible for these procedures.

In addition to the foregoing, various devices and systems of the presentdisclosure can be used to perform methods for retroperfusion of variousbodily organs to treat many different types of conditions. As referencedabove, providing blood from one bodily vessel to another bodily vesselcan be performed using devices and systems of the present disclosure,but in accordance with the following, said devices and systems can alsobe used to perform the following novel methods and procedures.

As generally referenced above, the concept of using veins to deliveroxygenated nutrient-filled blood (arterial blood) is predicated on thefact that despite any extent of the coronary arterial disease, thecorresponding venous counterpart is atherosclerosis-free. An additionalfact is that the upper body arterial system has much less predilectionfor atherosclerosis than the lower body. As such, the present disclosureidentifies that the upper body can generally serve as the source ofarterial blood to the venous systems of organs with arterial disease,and that devices and systems of the present disclosure can also be usedin that regard.

An additional characteristic of the venous system necessary tofacilitate SARP (as referenced herein) is the existence of a redundancyof the venous system (namely multiple veins per artery as well asinterconnections between venous vessels) to ensure proper venousdrainage when portion of the system is used for SARP.

In view of the foregoing, a number of embodiments for retroperfusion ofvarious organs or bodily regions that identify arterial blood donor andorgan (venous system) are identified with the present disclosure,including, but not limited to, the following:

(i). Peripheral vessels. Embodiments of devices and systems of thepresent disclosure can be used to provide oxygenated blood from thefemoral artery, the internal femoral artery, or the iliac artery, forexample, to the distal saphenous vein or to deep muscle veins forarterialization in diabetic patients (a diffuse disease) to treat, forexample a leg pre-amputation or a necrotic or gangrenous foot ulcer.This venous system has valves (typically larger than 1-1.5 mm indiameter) which can be overcome (inverted) through catheterization(namely the insertion of guidewire and SARP catheter, with guidewiredimensions down to 0.35 mm for 0.014″ standard guidewire) to facilitatesaid peripheral vessel treatment.

(ii). Kidney-Renal Vein. Embodiments of devices and systems of thepresent disclosure can also be used to facilitate arterialization of therenal vein, which can be partial (polar vein) or total (left or rightmain veins) by way of the femoral or iliac arteries (if disease free),or from the axillary, brachial, or subclavian arteries of the upperbody, if desired. Said procedure could be performed to, for example,treat acute or chronic renal ischemia due to diffuse atherosclerosis,severe intima hyperplasia, and to treat the kidney in connection withvarious collagen-vascular diseases.

(iii). Intestine (Bowel). A number of arterial sources, such as thefemoral, iliac, axiallary, brachial, subclavian, or epigastric arteries,can be used with devices and systems of the present disclosure tofacilitate regional arterialization following vein anastomosis (at thevein arch) to treat mesenteric arterial ischemia. In at least oneembodiment, said arterialization is performed to treat an acute embolicor thrombotic mesenteric artery occlusion in patients with a severebowel ischemia.

(iv). Spine. The first of the two main divisions of the spinal system,namely the intracranial veins, includes the cortical veins, the duralsinuses, the cavernous sinuses, and the ophthalmic veins. The secondmain division, namely the vertebral venous system (VVS), includes thevertebral venous plexuses which course along the entire length of thespine. The intracranial veins richly anastomose with the VVS in thesuboccipital region, and caudally, the cerebrospinal venous system(CSVS) freely communicates with the sacral and pelvic veins and theprostatic venous plexus. The CSVS constitutes a unique, large-capacity,valve-less venous network in which flow is bidirectional. The CSVS playsimportant roles in the regulation of intracranial pressure with changesin posture, and in venous outflow from the brain. In addition, the CSVSprovides a direct vascular route for the spread of a tumor, aninfection, or an emboli among its different components in eitherdirection. Various embodiments of devices and systems of the presentdisclosure can be used to provide oxygenated blood from the externalcarotid artery, the brachial artery, or the axiallary artery, directlyto the jugular vein to treat any number of potential spinal injuries orconditions, including spinal cord ischemia.

(v). Penis. Various embodiments of devices and systems of the presentdisclosure can also be used to provide arterial blood from theepigastric artery to the penile dorsal vein to the cavernous system ofthe penis to treat erectile dysfunction.

The foregoing examples of organ-specific perfusion protocols are notintended to be exhaustive, but merely exemplary of various novel uses ofperfusion devices and systems of the present disclosure. Accordingly,the present disclosure includes various methods for treatingorgan-related diseases, various methods of providing arterial(oxygenated) blood to veins at or near various organs, and variousmethods of potentially arterializing veins at or near various bodilyorgans using devices and systems of the present disclosure.

For example, and as shown in FIG. 19, an exemplary method of organperfusion of the present disclosure is provided. Method 1900, in atleast one embodiment, comprises the steps of positioning at least aportion of a device into a patient's artery (an exemplary arterypositioning step 1902), positioning at least a portion of the same or adifferent device into a patient's vein at or near a target organ (anexemplary vein positioning step 1904), and facilitating operation of thepositioned portions to allow blood to flow from the artery to the veinto treat a condition or disease of the target organ (an exemplaryoperation step 1906).

By way of example, an exemplary artery positioning step 1902 could beperformed by positioning at least part of a first catheter 10 having acannula 16 within an artery of a patient, the first catheter 10configured to permit arterial blood to flow therethrough and furtherconfigured to permit a portion of the arterial blood to flow through thecannula 16, and an exemplary vein positioning step 1904 could beperformed by positioning at least part of a second catheter 150 within avein of the patient at or near a target organ, the second catheter 150configured to receive some or all of the portion of the arterial blood.In such an embodiment, which may be referred to as a chronic treatmentusing catheter 10 and catheter 150, an exemplary operation step 1906involves connecting the cannula 16 of the first catheter 10 to a portionof the second catheter 150 so that some or all of the portion of thearterial blood flowing through the cannula 16 is provided into the veinto treat a condition or disease of the target organ.

Further, and by way of another example, an exemplary artery positioningstep 1902 could be performed by positioning at least a portion of anarterial tube 1032 of a perfusion system 100 within an artery of apatient, the arterial tube 1032 configured to permit arterial blood toflow therethrough, and an exemplary vein positioning step 1904 could beperformed by positioning at least a portion of a first catheter 1000 ofthe perfusion system 100 into a vein of the patient at or near a targetorgan, the first catheter 1000 configured to receive some or all of thearterial blood from the arterial tube 1032. In such an embodiment, whichmay be referred to as an acute treatment using system 100 of the presentdisclosure, an exemplary operation step 1906 involves operating a firstflow regulator 1036 of the perfusion system 100 so that some or all ofthe arterial blood flowing through the arterial tube 1032 is providedinto the vein to treat a condition or disease of the target organ.

In addition to the foregoing, an exemplary device for occluding aluminal organ of the present disclosure is shown in FIG. 20. As shown inFIG. 20, device 2000 comprises a coil 2002 configured to fit within adelivery mechanism 2004, such as a delivery catheter. Coil 2002, invarious embodiments, has at least two configurations, namely anuncompressed (or expanded) configuration and a compressed (or retracted)configuration, as shown in FIGS. 20 and 21, respectively. As referencedherein, the terms “uncompressed” and “expanded” are usedinterchangeably, and the terms “compressed” and “retracted” are usedinterchangeably. Delivery mechanism 2004, as shown in FIG. 20, isconfigured to fit within a mammalian luminal organ 2006, such as a vein,for use in connection with an arterialization procedure, for example.Furthermore, and in various embodiments, device 2000 comprises anon-coil device 2000, wherein the non-coil device 2000 has at least twoconfigurations, namely an expanded configuration and a retractedconfiguration, wherein the retracted configuration is capable ofoccluding a patient's luminal organ. The expanded configuration of coil2002, as generally referenced above, would not occlude the luminalorgan, while the retracted configuration of coil 2002, as noted above,would occlude the luminal organ.

Delivery of coil 2002 to a targeted location within a bodily vessel maybe facilitated by use of a pusher 2008, as shown in FIGS. 20 and 21.Pusher 2008, in various embodiments, comprises a shaft 2010 and anoptional tip 2012 configured to fit within delivery mechanism 2004 andto facilitate placement of coil 2002. Tip 2012, as shown in FIGS. 20 and21, may be relatively circular in shape so to prevent coil 2002 frommoving past pusher 2008 within delivery mechanism 2004.

Delivery mechanism 2004, as referenced above and shown in FIG. 20, maycomprise a catheter having a wall 2014 defining a lumen 2016therethrough. Coil 2002, in an expanded configuration, would fit withinlumen 2016 of delivery mechanism 2004 during delivery of coil 2002within a patient's body.

Coil 2002 may have any number of configurations. In at least oneembodiment, coil 2002 has a first configuration that has a relativelylinear configuration that is a native first configuration. In thepresent application, the term “native” refers to a configuration thatcoil 2002 has without any external assistance. For example, a nativefirst configuration of coil 2002 may be relatively stretched, and anative second configuration of coil 2002 may be relatively compressed.While an external device, such as a pusher 2008, may be used tofacilitate conversion from a native first configuration to a nativesecond configuration, coil 2002 would then remain in a secondconfiguration without any external forces or pressures used to maintainthe second configuration. Should a user of coil 2002 subsequently desireto convert coil 2002 back to a first configuration, external forces orpressures could be used to facilitate the conversion, and coil 2002would then again natively remain in a first configuration 2002 untilchanged once again.

FIGS. 22A and 22B show the delivery of a coil 2002 within a mammalianluminal organ, such as a cardiac vein. As shown in FIG. 22A, deliverymechanism 2004, coil 2002, and pusher 2008 are advanced into luminalorgan 2006, and after being positioned in a desired location, coil 2002can be delivered directly into luminal organ 2006, as shown in FIG. 22B,to occlude luminal organ 2006.

FIG. 22C shows the delivery of a coil within a patient's heart 2200. Asshown in FIG. 22C, delivery mechanism 2004, coil 2002, and pusher 2008are advanced into the patient's heart, through the coronary sinus 2202,and into the cardiac vein, so that coil 2002 can be delivered within thecardiac vein to occlude the same.

In various embodiments, coils 2002 are metallic memory coils (comprisingnitinol, stainless steel, and/or the like) having an optional coating2020 (as shown in FIG. 20) such as polytetrafluoroethylene (PTFE),polyethylene terephthalate (such as Dacron®, for example), polyurethane,and/or other biologically-compatible coatings. In at least oneembodiment, coil 2002 is radiopaque so that it can be identified withina patient's body using radiography, for example.

An exemplary coil occlusion system of the present disclosure is shown inthe block diagram of FIG. 23. As shown in FIG. 23, system 2300 comprisesan exemplary occlusion device 2000 of the present disclosure, a deliverymechanism 2004, and a pusher 2008. Occlusion device 2000 and pusher2008, when delivering occlusion device 2000, would be positioned withinlumen 2016 of delivery mechanism 2004. Prior to delivery of occlusiondevice 2000, an optional guidewire 2302 can be introduced into a patientso that delivery mechanism 2004, or a portion thereof, can be advancedover guidewire 2302 to facilitate the ultimate delivery of occlusiondevice 2000.

An exemplary method of using an exemplary occlusion device 2000 of thepresent disclosure to occlude a luminal organ is described as followsand as shown in the block diagram of method steps shown in FIG. 24. Inat least one embodiment of method 2400 of the present disclosure, method2400 comprises the steps of introducing an exemplary occlusion device2000 of the present disclosure into a patient's body (an exemplaryintroduction step 2402), which may be performed by advancing a deliverymechanism 2004 into a patient's body with our without the priorinsertion of a guidewire 2302 to facilitate delivery. Method 2400, asshown in FIG. 24, may then comprise the step of advancing at least partof delivery mechanism 2004 to a desired location within a patient (anexemplary delivery mechanism advancement step 2404), such as, forexample, a patient's vein. In at least one embodiment, method 2400comprises the step of advancing an occluder device 2000 positionedwithin delivery mechanism 2004 (an exemplary occluder device advancementstep 2406) directly into the patient's luminal organ (outside ofdelivery mechanism) using, for example, pusher 2008. Occluder deviceadvancement step 2406 may itself also include the step of compressingoccluder device 2000 or otherwise facilitating a configuration changefrom a first uncompressed or otherwise non-occlusive configuration to asecond compressed or otherwise occlusive configuration (an exemplarycompression step 2408), or compression step 2408 may be performed afteroccluder device advancement step 2406. Compression step 2408 isperformed so that occluder device 2000 effectively occludes the luminalorgan percutaneously. After compression step 2408, delivery mechanism2004 and pusher 2008 may be withdrawn from the patient's body (anexemplary delivery mechanism withdrawal step 2410), whereby occluderdevice 2000 remains within a patient's luminal organ, occluding thesame.

Performance of method 2400, as referenced herein, may be in conjunctionwith a potential arterialization and/or retroperfusion method. Mammals(humans and animals) have a venous system comprising an excessnumber/amount of veins, i.e., drainage through the venous system can bemade through any number of channels. Arterialization, a term generallyused to describe a change of a part of a vein to a part of an artery,includes gradual thickening of the venous wall over time so that thearterialized vein can withstand the higher pressures of the arterialsystem if the arterialized vein were to be grafted into the arterialsystem. Subjecting a non-arterialized venous vessel to the highpressures of arterial blood flow typically results in rupture of thevenous vessel. With certain corresponding retroperfusion therapies, forexample, the pressure of the arterial blood flow is at least initiallycontrolled such that the venous vessel can arterialize prior to beingsubjected to the unregulated pressure of the arterial blood flow.

Descriptions of arterialization and retroperfusion are referenced inother applications of Kassab, including PCT/US08/87863, filed Dec. 19,2008, U.S. Ser. No. 13/125,512, filed Apr. 21, 2011, and U.S. Ser. No.13/092,803, filed Apr. 22, 2011, the entire contents of which are herebyincorporated into the present disclosure by reference in their entirety.

In view of the same, an exemplary method 2400 may further include thesteps of excising an arterialized vein from the patient's venous system(an exemplary excision step 2412) and grafting the arterialized veininto the patient's arterial system (an exemplary grafting step 2414), asshown in FIG. 24. Excision step 2412 would occur a period of time afteroccluder device 2000 has been positioned within a vein, as the increasedpressure of the vein at or near the occlusion would promote veinarterialization. Excision step 2412 and grafting step 2414 may beperformed in connection with a coronary bypass procedure, for example.An exemplary method 2400 may further comprise the general step ofperforming a retroperfusion procedure (as referenced in one or more ofPCT/US08/87863, filed Dec. 19, 2008, U.S. Ser. No. 13/125,512, filedApr. 21, 2011, and U.S. Ser. No. 13/092,803, filed Apr. 22, 2011) (anexemplary retroperfusion step 2416) during coil occlusion and/or afterexemplary excision step 2412.

While various embodiments of coil occlusion devices and systems andmethods of using the same have been described in considerable detailherein, the embodiments are merely offered as non-limiting examples ofthe disclosure described herein. It will therefore be understood thatvarious changes and modifications may be made, and equivalents may besubstituted for elements thereof, without departing from the scope ofthe present disclosure. The present disclosure is not intended to beexhaustive or limiting with respect to the content thereof.

Further, in describing representative embodiments, the presentdisclosure may have presented a method and/or a process as a particularsequence of steps. However, to the extent that the method or processdoes not rely on the particular order of steps set forth therein, themethod or process should not be limited to the particular sequence ofsteps described, as other sequences of steps may be possible. Therefore,the particular order of the steps disclosed herein should not beconstrued as limitations of the present disclosure. In addition,disclosure directed to a method and/or process should not be limited tothe performance of their steps in the order written. Such sequences maybe varied and still remain within the scope of the present disclo sure.

1. An occluder system, comprising: an occluder device comprising a coilhaving at least a first, uncompressed configuration and a second,compressed configuration, wherein the coil in the first, uncompressedconfiguration is configured to fit within a delivery mechanism sized andshaped to fit within a mammalian luminal organ, and wherein the coil inthe second, compressed configuration is configured to occlude amammalian luminal organ.
 2. The system of claim 1, further comprising: adelivery mechanism sized and shaped to fit within the mammalian luminalorgan, the delivery mechanism configured to receive the coil in thefirst, uncompressed configuration within a lumen defined within thedelivery mechanism.
 3. The system of claim 2, further comprising: apusher configured to fit within the lumen of the delivery mechanism andfurther configured to facilitate placement of the coil in the second,compressed configuration within the mammalian luminal organ to occludethe mammalian luminal organ.
 4. The system of claim 3, furthercomprising: a guidewire configured to fit within the mammalian luminalorgan and further configured to fit within the lumen of the deliverymechanism.
 5. The system of claim 3, wherein the pusher comprises ashaft and a tip, wherein the tip is relatively or completely circular inshape and configured to prevent the coil from moving past the pusherwithin the delivery mechanism.
 6. The system of claim 2, wherein thedelivery mechanism comprises a delivery catheter having a wall anddefining a lumen therethrough.
 7. The system of claim 1, wherein thecoil is capable of changing from the first, uncompressed configurationto the second, compressed configuration and back to the first,uncompressed configuration.
 8. The system of claim 1, wherein the coilcomprises a material selected from the group consisting of nitinol,stainless steel, and a radiopaque material.
 9. The occluder device ofclaim 1, wherein the coil is at least partially coated by a materialselected from the group consisting of polytetrafluoroethylene,polyethylene terephthalate, and polyurethane.
 10. An occluder system,comprising: an occluder device comprising a coil having at least afirst, uncompressed configuration and a second, compressedconfiguration; a delivery mechanism sized and shaped to fit within themammalian luminal organ, the delivery mechanism configured to receivethe coil in the first, uncompressed configuration within a lumen definedwithin the delivery mechanism; and a pusher configured to fit within thelumen of the delivery mechanism and further configured to facilitateplacement of the coil in the second, compressed configuration within themammalian luminal organ; wherein the coil in the second, compressedconfiguration is configured to occlude the mammalian luminal organ. 11.The system of claim 10, wherein the pusher comprises a shaft and a tip,wherein the tip is relatively or completely circular in shape andconfigured to prevent the coil from moving past the pusher within thedelivery mechanism.
 12. A method of using an occluder device, the methodcomprising the steps of: introducing an occluder device into a patient'sbody, the occluder device comprising a coil having at least a first,uncompressed configuration and a second, compressed configuration,wherein the coil in the first, uncompressed configuration is configuredto fit within a delivery mechanism sized and shaped to fit within amammalian luminal organ, and wherein the coil in the second, compressedconfiguration is configured to occlude a mammalian luminal organ, theocclusion device positioned within a lumen of the delivery mechanism;advancing at least part of the delivery mechanism to a desired locationwithin the patient's body; advancing the occluder device directly into aluminal organ within the patient's body; and compressing the occluderdevice within the luminal organ to occlude the luminal organ.
 13. Themethod of claim 12, wherein the introducing step includes the steps ofintroducing a guidewire into the patient's body, advancing the deliverymechanism into the patient's body over the guidewire, and removing theguidewire from the patient's body.
 14. The method of claim 12, whereinthe introducing step is performed to introduce the occluder devicewithin the delivery mechanism into a vein.
 15. The method of claim 12,wherein the step of advancing the occluder device directly into theluminal organ is performed by using a pusher positioned within thedelivery mechanism to advance the occluder device.
 16. The method ofclaim 12, wherein the step of compressing the occluder device within theluminal organ is performed by using a pusher positioned within thedelivery mechanism to compress the occluder device
 17. The method ofclaim 12, wherein the step of compressing is performed to facilitate aconfiguration change of the occluder device from the first, uncompressedconfiguration to the second, compressed configuration.
 18. The method ofclaim 14, further comprising the steps of: excising an arterialized veinfrom the patient's body, the arterialized vein located at or near theoccluder device within the vein; and grafting the arterialized vein intothe patient's arterial system.
 19. The method of claim 18, furthercomprising the step of: performing a retroperfusion procedure while theoccluder device is in the second, compressed configuration within theluminal organ and/or after the step of excising the arterialized vein.20. The method of claim 12, wherein the step of advancing at least partof the delivery mechanism to a desired location within the patient'sbody is performed using a technique selected from the group consistingof (i) advancing at least part of the delivery mechanism into a heart ofthe patient, through a coronary sinus, and into a cardiac vein, and (ii)advancing the occluder device directly into the cardiac vein.